NEUROSCIENCES AND NEUROANAESTHESIA
Dexmedetomidine,an a 2-adrenergic agonist,inhibits neuronal
delayed-recti?er potassium current and sodium current
B.-S.Chen 13,H.Peng 2and S.-N.Wu 12*
1Institute of Basic Medical Sciences and 2Department of Physiology,National Cheng Kung University Medical College,No.1,University Road,Tainan 70101,Taiwan,Republic of China.3Department of
Anesthesiology,Buddhist Dalin Tzu Chi General Hospital,Chiayi County,Taiwan,Republic of China
*Corresponding author.E-mail:snwu@https://www.doczj.com/doc/272038226.html,.tw
Background.Dexmedetomidine (DEX),a selective agonist of a 2-adrenergic receptors,is
recognized to facilitate analgesia and anaesthesia in humans.Despite the potential for wide
use,its effects on ion currents and membrane potential in neurones remain largely unclear.
Methods.W e investigated the effects of DEX on ion channels in NG108-15neuronal cells dif-
ferentiated with dibutyryl cyclic AMP and in cultured cerebellar neurones.
Results.DEX suppressed the amplitude of delayed recti?er K +current [I K(DR)]in a concen-
tration-dependent manner with an IC 50value of 4.6m M in NG108-15cells.No change in the
steady-state inactivation of I K(DR)was evident in the presence of DEX.A minimal binding
scheme was also used to evaluate DEX-induced block of I K(DR).Inhibition of I K(DR)by DEX
was still observed in cells preincubated with yohimbine (10m M)or efaroxan (10m M).DEX
depressed the peak amplitude of Na +current (I
Na ),whereas it had minimal effect on L-type
Ca 2+current.Under current-clamp con?guration,DEX increased the duration of action poten-
tials (APs).I K(DR)and I Na in response to AP waveforms were more sensitive to block by DEX
than those elicited during rectangular pulses.In isolated cerebellar granule cells,DEX also
effectively suppressed I K(DR).
Conclusions.The effects of DEX are not limited to its interactions with a 2-adrenergic recep-
tors.Inhibitory effects on I K(DR)and I Na constitute one of the underlying mechanisms through
which DEX and its structurally related compounds might affect neuronal activity in vivo .
Br J Anaesth 2009;103:244–54
Keywords :ions,ion channels,pharmacology;ions,ion channels,voltage-gated;model,
neuroblastoma cells;pharmacology,dexmedetomidine
Accepted for publication:April 7,2009
Dexmedetomidine (DEX)is a potent and highly selective agonist of the a 2-adrenergic receptors that is approved by the US Food and Drug Administration for the provision of short-term sedation of adult patients in the intensive care unit.It exerts a variety of actions on the human brain,including sedation,anaesthetic-sparing effects,and analge-sia.12Because this agent has minimal effects on venti-lation,it is relatively safe in the setting of functional neurosurgery.3Its sedative action is thought to involve inhibition of the locus coeruleus and subsequent disinhibi-tion of the ventrolateral preoptic nucleus.4DEX has been reported to decrease the convulsive potency of bupivacaine and levobupivacaine in awake rats.5A recent study showed that as an anaesthetic adjunct,DEX at a high concentration can affect transcranial motor evoked responses.6However,there are limited reports regarding its ionic mechanism of action on neurones.
Recent evidence has emerged that the effects on ion channels may be an important mechanism underlying DEX-induced actions in neurones.For example,previous studies demonstrated the ability of DEX to modify L-type Ca 2+current (I Ca,L )in pheochromocytoma cells 7and to inhibit M 3muscarinic receptors in dorsal root ganglion cells.8In paraventricular nucleus neurones or substantia gelatinosa neurones,DEX increases G-protein-coupled inwardly recti-fying K +current
and inhibits hyperpolarization-elicited inward current.910Voltage-gated K +(K V )channels play an essential role in determining the excitability of neurones.#The Author [2009].Published by Oxford University Press on behalf of The Board of Directors of the British Journal of Anaesthesia.All rights reserved.
British Journal of Anaesthesia 103(2):244–54(2009)
doi:10.1093/bja/aep107Advance Access publication June 20,
2009
Among them,delayed recti?er K +(K DR )channels are ubi-quitous in neurones.In fast-spiking neurones,a causal relationship between K V 3,especially K V 3.1,and the delayed recti?er K +current [I K(DR)]has been well estab-lished.The K V 3recombinant channel has properties suit-able for the generation of high-frequency ?ring.High activation threshold (about 220mV)and fast deactivation
kinetics of the channels make them ideal for narrowing
spike width and inter-spike interval.11The I K(DR)containing
K V 3subunits contributes to changes in membrane potential in differentiated NG108-15cells.12–14Previous studies in our laboratory have shown that tra-madol suppresses the amplitude of I K(DR)in NG108-15
cells.14If K V 3-encoded K +currents are located at nerve terminals,modulation of current amplitude might be expected indirectly to alter Ca 2+in?ux and to affect neuro-transmitter release in the absence of overt changes in ?ring patterns.1115However,whether DEX can interact with I K(DR)or other types of ion currents to modify mem-brane potential in neurones remains largely unclear,despite its clinical use in a variety of neurosurgical pro-cedures.2–4In this study,we investigated the effects of DEX on ion currents (e.g.delayed recti?er K +current [I K(DR)],Na +current [I Na ],and L-type Ca 2+current [I Ca,L ])and mem-brane potential in NG108-15neuronal cells differentiated with dibutyryl cyclic AMP and in cultured cerebellar neur-ones.DEX was able to suppress both I K(DR)and I Na .The major action of DEX on I K(DR)is thought to be through an
open-channel mechanism.These inhibitory effects are not mediated by a 2-adrenergic receptors and might contribute
to its pharmacological actions in vivo .Methods Drugs and solutions DEX (dexmedetomidine HCl;(S )-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole hydrochloride;Precedex w )was obtained from Abbott Laboratories (Abbott Park,IL,USA).Collagenase,dibutyryl cyclic AMP,DNase I,efaroxan,tetraethylammonium chloride,and tetrodotoxin were purchased from Sigma Chemicals (St Louis,MO,USA),and yohimbine was from Tocris (Bristol,UK).Tissue culture media,L -glutamine penicillin–streptomycin,fungi-
zone,and trypsin were obtained from Life Technologies (Carlsbad,CA,USA).All other chemicals,including CsCl 2and CdCl 2,were commercially available and of reagent grade.The composition of normal Tyrode’s solution was 136.5mM NaCl,5.4mM KCl,1.8mM CaCl 2,0.53mM MgCl 2,5.5mM glucose,and 5.5mM HEPES–NaOH buffer,pH 7.4.To record I K(DR)or membrane potential,the patch pipette was ?lled with a solution consisting of 140mM KCl,1mM MgCl 2,3mM Na 2ATP,0.1mM Na 2GTP,0.1mM EGTA,and 5mM HEPES–KOH buffer,pH 7.2.To measure I Na or I Ca,L ,K +ions inside the pipette solution were replaced with equimolar Cs +ions,and the pH was adjusted to 7.2with CsOH.In some experiments,the pipette was ?lled with the solution which contained 10m M DEX.
Cell preparation and differentiation
The clonal strain NG108-15cell line,formed by Sendai
virus-induced fusion of the mouse neuroblastoma clone
N18TG-2and the rat glioma clone C6BV-1,was obtained from the European Collection of Cell Cultures
(ECACC-88112302;Wiltshire,UK).Cells
were kept in monolayer cultures at a density of 106ml 21in plastic disks containing Dulbecco’s modi?ed Eagle’s medium supplemented with 100m M hypoxanthine,1m M amino-
pterin,16m M thymidine,and 5%fetal bovine serum as
the culture medium,in a humidi?ed incubator equilibrated with 90%air/10%CO 2at 378C.14Media were replenished every 2–3days with fresh media.To induce neuronal differentiation,culture medium was replaced with medium containing 1mM dibutyryl cyclic AMP and cells were cultured in the incubator for 1–7days.16In a separate set of experiments,differentiated NG108-15cells were prein-cubated with yohimbine (10m M)or efaroxan (10m M)for 5h before electrophysiological experiments were performed.
Isolation of cerebellar granule cells
Cerebellar granule cells were isolated from Wistar rat pups
of post-natal days 9–10.Cerebella of 5–7animals were
excised after decapitation,and minced and digested with
collagenase (50mg ml 21)for 10min.Mechanical tritura-
tion with a Pasteur pipette was made in a DNase I/soybean
trypsin inhibitor solution.Dissociated cells were centri-
fuged and suspended in normal Tyrode’s solution.Cells were used for experiments within 2–3h after isolation.Animal experiments were conducted according to the pro-tocols that follow the NIH standards and the guidelines for the Care and Use of Experimental Animals.The procedure was approved by the Animal Care and Use Committee of the National Cheng Kung University,Tainan,Taiwan,Republic of China.
Electrophysiological measurements
Immediately before each experiment,cells were disso-ciated and an aliquot of cell suspension was transferred to a recording chamber mounted on the stage of an inverted DM-IL microscope (Leica,Wetzlar,Germany).Cells were bathed at room temperature (20–258C)in normal Tyrode’s
solution containing 1.8mM CaCl 2.Patch pipettes were
pulled from Kimax-51glass capillaries (Kimble Glass,Vineland,NJ,USA)on a PP-830microelectrode puller (Narishige,Tokyo,Japan),and their tips were ?re-polished
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with an MF-83microforge (Narishige).The resistances of the patch pipettes when ?lled with the internal solutions were between 3and 5M V .Ion currents were measured with glass pipettes in a whole-cell con?guration of the patch-clamp technique,using an RK-400patch-clamp ampli?er (Biologic,Claix,France).1317Data recordings and analyses Signals were displayed on an HM-507oscilloscope (Hameg Inc.,East Meadow,NY,USA).Data were stored online in a Slimnote VX 3computer (Lemel,Taipei,
Taiwan)at 10kHz equipped with a Digidata-1322A inter-face (Molecular Devices,Sunnyvale,CA,USA).Series resistance,in the range of 5–15M V ,was electronically compensated.Data were analysed by the use of pCLAMP
9.0software (Molecular Devices),Origin 7.5software
(Microcal Software,Northampton,MA,USA),or custom-made macros built in Excel 2007spreadsheet running on
Windows Vista (Microsoft,Redmond,WA,USA).The
pCLAMP-generated voltage-step protocols were used to measure the current–voltage (I–V )relations for ion cur-rents.Action potential duration (APD)was measured at 90%of repolarization (APD 90).To evaluate the percentage inhibition of DEX on I K(DR),NG108-15cells were bathed in normal Ca 2t-free Tyrode’s solution and each cell was depolarized from 250to +50mV.The amplitude of I K(DR)at the end of depolarizing pulse during exposure to different concentrations (0.1–30m M)of DEX was measured.Concentration–response data for inhibition of I K(DR)were ?tted with a modi?ed form of the Hill equation:y ?e1àa T??DEX àn H
?DEX àn H tIC àn H 50ta ;where y is the normalized amplitude of I K(DR);[DEX]rep-resents the DEX concentration;and IC 50and n H are the concentration required for 50%inhibition and Hill coef?-cient,respectively.Maximal inhibition (i.e.12a )was also estimated.By the use of a least squares method,the smooth curve shown in Figure 1B was allowed to converge on the experimental data when the maximal block was left unde?ned.Time constants of current activation (t act )in the absence or presence of DEX were determined by ?tting
the trajectory of each current trace with single exponential
curves.To determine the effect of DEX on the steady-state inactivation of I K(DR),the relationship between the con-ditioning potentials and the normalized amplitude of I K(DR)obtained with or without addition of DEX (3m M)was ?tted by the Boltzmann function:I ?I max 1texp eV àa =b Twhere I max represents the maximal activated I K(DR),V is the membrane potential in mV,a the membrane potential for a half-maximal inactivation,and b the slope factor of the inactivation curve of I K(DR).
Values are provided as means (SEM )with sample sizes (n )indicating the number of cells from which the data were taken.The paired or unpaired Student’s t -test and
one-way analysis of variance (ANOV A )with the least signi?-
cant difference method for multiple comparisons were used for the statistical evaluation of differences among means.Non-parametric Kruskal–Wallis test was then used,if the assumption of normality underlying ANOVA was
violated.Statistical analyses were performed using SPSS 14.0(SPSS Inc.,Chicago,IL,USA).Statistical signi?-cance was determined at a P -value of ,0.05.
Results
Effect of DEX on delayed recti?er K +current [I K(DR)]in differentiated NG108-15cells
In an initial set of experiments,a whole-cell con?guration of the patch-clamp technique was used to evaluate the effects of DEX on ion currents in NG108-15cells differ-entiated with dibutyryl cyclic AMP (1mM).To record I K(DR),cells were bathed in Ca 2+-free Tyrode’s solution which contained tetrodotoxin (1m M)and CdCl 2(0.5mM),and the recording pipette was ?lled with a K +-containing solution.Figure 1shows that DEX can depress the amplitude of I K(DR)in a concentration-dependent manner.In these experiments,each cell was
depolarized from 250to +50mV with a duration of 300
ms,and current amplitudes of I K(DR)were measured at the
end of depolarizing pulses.DEX (0.1–30m M)suppressed
the amplitude of I K(DR)in a concentration-dependent
manner.The relationship between the DEX concentration and the percentage inhibition of I K(DR)was constructed and plotted in Figure 1B .The IC 50value for DEX-induced inhibition of I K(DR)was 4.6m M.Figure 1C illustrates aver-aged I–V relationships of I K(DR)obtained in the control and during cell exposure to 3m M DEX.The results demonstrate that DEX has a signi?cant depressant action on I K(DR)functionally expressed in differentiated NG108-15cells.
Kinetic studies of DEX-induced block of I K(DR)Because the activation time course of I K(DR)during exposure to DEX tends to be progressively reduced,it is important to determine the kinetics of DEX-induced block in these cells.As shown in Figure 1D ,when cells were
depolarized from 250to +50mV,exposure to DEX was
noted to produce a reduction of t act in a concentration-
dependent fashion.Therefore,the results suggest that the
inhibitory effects of DEX on I K(DR)can be primarily
explained by state-dependent blocker where it can bind to
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the open state of the channel according to the minimal kinetic scheme:18C O O · D
where a and b are kinetic constants for the opening and
closing of the channel,k 1and k 21are those for forward and reverse rate constants of DEX binding,and D is the
DEX concentration.C,O,and O .D represent the closed,open,and open-bound states,respectively.Forward and reverse rate constants,k 1and k 21,were estimated from the values of t
act for DEX-induced change in the trajectory of
I K(DR)(Fig.1E ).The values were calculated using the
relation:
t à1?k 1??D tk à1
In particular,k 1and k 21,respectively,result from the slope and from the y -axis intercept at [D ]=0of the linear p A 1000020003000–50050m V [DEX] (μM)
D A C u r
r e n t a m p l
i t u
d
e (
p
A
)
ms 002000e d c b a pA 2040Time (ms)Fig 1Inhibitory effect of DEX on I K(DR)in NG108-15cells differentiated with dibutyryl cyclic AMP.Cells were bathed in Ca 2+-free Tyrode’s solution that contained tetrodotoxin (1m M)and CdCl 2(0.5mM).(A )Superimposed current traces obtained in the absence and presence of DEX.The upper part indicates the voltage protocol used.Inset shown in the right side of (A )indicates expanded time scale of current traces (dashed box).a,control;b,0.1m M DEX;c,0.3m M DEX;d,1m M DEX;and e,3m M DEX.(B )Concentration–response relationship for DEX-induced inhibition of I K(DR).Each cell was depolarized from 250to 50mV.Each point represents the mean (SEM )value (n =6–9).The smooth line represents the best ?t to the Hill equation as described in Methods.The IC 50value was derived from the non-linear curve ?t.The IC 50value,maximally inhibited percentage of I K(DR),and Hill coef?cient (n H )were 4.6m M,90%(i.e.a =0.1),and 1.1,respectively.(C )Averaged I–V relationships of I K(DR)obtained in the absence and presence of 3m M DEX.Mean (SEM )(n =7–12).In (D ),the time courses of current activation in the absence and presence of DEX were well ?tted by a single exponential.a,control;b,0.1m M DEX;c,0.3m M DEX;d,1m M DEX;and e,3m M DEX.The inset indicates the voltage protocol used.In (E ),the reciprocal of the activation time constant (t act ),obtained by a single-exponential ?t of the increasing phase of I K(DR),was plotted against the DEX concentration.Data points were ?tted by a linear regression,suggesting that the interaction occurs with a stoichiometry of 1.Forward (k 1)and reverse (k 21)rate constants,given by the slope and the y -axis intercept of the interpolated line,were 0.056ms 21m M 21and 0.34ms 21,respectively.Each point represents the mean (SEM )value (n =8–11).
Dexmedetomidine inhibits neuronal ion currents
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regression interpolating the reciprocal of time constants (i.e.t 21)vs different DEX concentrations (i.e.[D ]).In agreement with this kinetic scheme,the relationship between k 1and [D ]was found to be linear with a corre-
lation coef?cient of 0.95(Fig.1E ).The forward and reverse rate constants obtained from 6to 8different cells were calculated to be 0.056ms 21m M 21and 0.34ms 21,respectively.On the basis of these rate constants,a value of 6.1m M for the dissociation constant (K D =k 21?k 121)of
this drug was derived.Notably,this value was found to agree with its IC 50value determined from the concen-
tration–response curve (Fig.1B ).However,the backward rate constant (i.e.k 21)showed little dependence on the
DEX concentration:k 21was 0.34ms 21(n =6)at 1m M
and 0.34ms 21(n =6)at 3m https://www.doczj.com/doc/272038226.html,ck of effect of DEX on steady-state inactivation curve of I K(DR)To characterize the inhibitory effect of DEX on I K(DR),we
next investigated whether this drug affects the steady-state inactivation curve of I K(DR)in differentiated NG108-15
cells.Figure 2illustrates the steady-state inactivation curve of I K(DR)obtained in the absence and presence of DEX
(3m M).In these experiments,a 10s conditioning pulse to different membrane potentials preceded the test pulse to +50mV from a holding potential of 250mV.The
relationships between the conditioning potentials and the
normalized amplitudes of I K(DR)with or without appli-cation of DEX (3m M)were plotted and ?tted by the Boltzmann equation as described in Methods.In control,a =212.3(2.2)mV,b =6.6(0.8)mV (n =6),whereas in the presence of DEX (3m M),a =212.1(2.1)mV,b =6.3(0.7)mV (n =6).The values for a and b were not signi?cantly modi?ed in the presence of DEX (3m M),although it reduced the maximal conductance of I K(DR)by about 50%.Effect of DEX on averaged I–V relations of I K(DR)in NG108-15cells treated with yohimbine
DEX was reported to be a selective agonist of
a 2-adrenergic receptors.1Previous studies showed the ability of yohimbine to reverse both increased K +outward
currents and anticonvulsant effect caused by DEX.5910
We next evaluated whether inhibition of a -adrenergic receptors can in?uence DEX-induced block of I K(DR)in
NG108-15cells.In these experiments,differentiated NG108-15cells preincubated with yohimbine (10m M)for
5h.Yohimbine is an a 2-adrenoceptor antagonist,whereas efaroxan is an antagonist of imidazoline-I 1and a 2-
adrenergic receptors.In yohimbine-treated cells,the
inhibitory effect of DEX on the I–V relationship of I K(DR)
remained unaltered (Fig.3).No signi?cant difference in
the magnitude of DEX-induced inhibition of I K(DR)
between control cells and cells treated with DEX can be seen.Moreover,subsequent application of yohimbine (10m M)or efaroxan (10m M)did not reverse the inhibition of
I K(DR)caused by DEX (3m M)(data not shown).Similarly,in cells treated with efaroxan (10m M)for 5h,the magnitude of DEX-induced inhibition of I K(DR)remained unchanged.These results are thus interpreted to mean that the inhibitory effect of DEX on I K(DR)in these cells is unrelated to its binding to a 2-adrenergic receptors.Effect of DEX on voltage-gated Na +current (I Na )in differentiated NG108-15cells
We next investigated whether DEX has any effects on I Na present in these cells.Cells were bathed in Ca 2+-free Tyrode’s solution containing 0.5mM CdCl 2and the pipette was ?lled with a Cs +-containing solution.The effect of DEX on I Na was examined at different potentials and an I–V relationship of I Na was constructed.As shown
I
/
I
m a
x
Conditioning potential (mV)
B
C u r r
e n t
a m p
l
i t
u
d e
(p
A )010 000Time (ms)500020 00015 0000100020003000A ms 0
–50050mV 10000Fig 2Steady-state inactivation curve of I K(DR)in the absence or presence of DEX in differentiated NG108-15cells.Conditioning voltage pulses with a duration of 10s to potentials between 260and +60mV were applied from a holding potential of 250mV.After each conditioning pulse,a test pulse to +50mV was applied to evoke I K(DR).An example of current traces obtained by two-pulse protocol in the control is illustrated in (A ).The inset shown in (A )indicates the voltage protocol used.(B )Steady-state inactivation curve of I K(DR)obtained with or without application of DEX (3m M).The normalized amplitude of I K(DR)(I /I max )was constructed against the conditioning potentials,and the smooth curves were ?tted by the Boltzmann equation (see text for details).Mean (SEM )(n =5–9).Note that the steady-state inactivation curves of I K(DR)in the absence and presence of DEX are virtually superimposable.
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in Figure 4,DEX at a concentration of 10m M could signi?cantly decrease the peak amplitude of I Na ,when
cells were depolarizing from 280mV to different poten-tials ranging from 280to +40mV.For example,when the cell was depolarized from 280to 240mV,application of DEX (10m M)signi?cantly decreased I Na from 0.79(0.07)
to 0.62(0.07)nA (n =7).After washout of the drug,I Na
was returned to 0.76(0.06)nA (n =6).However,the overall I–V con?guration of I Na did not differ between the
absence and the presence of DEX.A subsequent appli-cation of yohimbine (10m M)did not reverse the inhibition of I Na caused by DEX (data not shown).Lack of effect of DEX on L-type Ca 2+current (I Ca,L )
in differentiated NG108-15cells
Previous reports showed that DEX is able to modify Ca 2+current in phaeochromocytoma cells.7We also determined the ability of this agent to alter the amplitude of I Ca,L in
these cells.The experimental results are illustrated in
Figure 5.When the cell was depolarized from 240to different potentials ranging from 240to +40mV,the
peak amplitude of I Ca,L was not found to differ between the absence and the presence of 10m M DEX.Moreover,when cells were exposed to this agent,no modi?cation of
the I–V relationship of I Ca,L can be demonstrated.
Therefore,unlike I Na ,I Ca,L is relatively insensitive to inhi-
bition by DEX in these cells.
Effect of DEX on action potentials in differentiated NG108-15cells
In another set of experiments,we determined the ability of
DEX to alter membrane potential.In these experiments,cells were bathed in normal Tyrode’s solution containing 1.8mM CaCl 2,and current-clamp recordings were made
in a K +-containing pipette solution.The resting membrane
potential and APD measured at 90%repolarization
(APD 90)in differentiated NG108-15cells were 270(8)
mV and 119(20)ms,respectively (n =21).A representative
example of DEX-induced effects on action potentials
(APs)in differentiated NG108-15cells is illustrated in
Figure 6.DEX at a concentration of 10m M signi?cantly decreased the amplitude of APs from 86(3)to 75(3)mV and prolonged the duration of APs from 76(9)to 143(21)ms (n =7).However,no discernible change in resting mem-brane potential can be demonstrated in the presence of C u r
r
e n t
a m
p l i
t
u
d e
(n A
)m V Control DEX
Time (ms)
050100150Fig 4Inhibitory effect of DEX on I Na in differentiated NG108-15neuronal cells.Cells were bathed in Ca 2+-free Tyrode’s solution containing 10mM tetraethylammonium chloride and 0.5mM CdCl 2.The recording pipette was ?lled with a Cs +-containing solution.(A )Superimposed current traces when the cell was depolarized from 280mV to different potentials.Upper panel is the control,and lower panel was obtained 2min after application of 10m M DEX.The uppermost part indicates the voltage protocol used.(B )Averaged I–V relationships of peak
I Na obtained in the absence or presence of 10m M DEX.Mean (SEM )(n =6–11).DEX reduced the peak amplitude of I Na with no change in the overall I–V con?guration.
C u
r r
e n t
a
m p
l
i t
u d e
(
p A )
Membrane potential (mV)Fig 3Effect of DEX on averaged I–V relationships of I K(DR)in
NG108-15cells treated with yohimbine.Before each experiment,cells were preincubated with yohimbine (10m M)for 5h.In each cell examined,I K(DR)was elicited from 250mV to different potentials ranging from 250to +50mV with 10mV increments.The I–V relationships of I K(DR)obtained in the absence or presence of 3m M DEX are illustrated.Mean (SEM )(n =5–10).Dexmedetomidine inhibits neuronal ion currents
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DEX.The widening of APs caused by DEX could be pri-marily explained by its block of I K(DR)and I Na ,but not by the activation of I Ca,L .Inhibitory effects of DEX on ion currents in response to AP waveforms in differentiated NG108-15cells The size and time course of ion currents [e.g.I Na and
I K(DR)]in response to change in AP waveforms tend to be
different from those elicited by rectangular voltage-clamp pulses.The effects of DEX on ion currents during APs generated from NG108-15cells were also investigated.In these experiments,cells were bathed in normal Tyrode’s solution,and the waveforms of APs were digitally gener-ated as voltage templates and replayed to evoke ion cur-rents.19As shown in Figure 7,the amplitudes of I Na and
I K(DR)in response to AP waveforms were reduced in the
presence of DEX.For example,after application of 1m M
DEX,the peak amplitude of I Na elicited by the waveforms of APs was decreased by about 10%.Moreover,I K(DR)in response to AP waveforms was suppressed by about 30%.The results led us to suggest that I Na and I K(DR)evoked by AP waveforms are more sensitive to block by this agent than those during rectangular pulses.Effect of DEX on I K(DR)in isolated rat cerebellar
granule cells Previous studies have demonstrated the presence of I K(DR)(i.e.K V 3.3-encoded current)in cerebellar granule cells.20DEX was shown to in?uence the cyclic GMP effector system in the mouse cerebellum.21Therefore,to verify whether the DEX-induced inhibition of I K(DR)could also be observed in another type of cells,we also investigated
the effect of DEX on I K(DR)in isolated cerebellar granular
cells.In isolated cerebellar granule cells,the I K(DR),which was clearly identi?ed as a slowly inactivating I K(DR),could be elicited.As shown in Figure 8,DEX was effec-
tive in suppressing I K(DR)found in these cells.When depolarizing pulses from –50to +50mV were applied,DEX (30m M)signi?cantly decreased current amplitude at the end of the voltage pulses from 2018(152)to 1196(81)pA (n =7).Consistent with the observations made in differentiated NG108-14cells,these data indicate that DEX is capable of inducing the block of I K(DR)and
increasing current activation in cerebellar granule cells.
Discussion
The present results demonstrate that in differentiated NG108-15neuronal cells,DEX produces a depressant action on I K(DR)in a concentration-and state-dependent fashion.DEX also blocks the peak amplitude of I Na ,whereas it had little or no effect on I Ca,L .This study
suggests that the exposure to this agent can produce inhibi-
tory effects on I K(DR)and I Na .In addition to activation of
a 2-adrenergic receptors,DEX-induced block of these cur-
rents could thus be potential mechanisms through which it
may depress neuronal excitability.
A notable feature of the block of I K(DR)by DEX in NG108-15cells is that the activating phase of the current C u r
r e
n t
a
m p l i
t u d e (p A
)m V
Control DEX Time (ms)
Fig 5Lack of effect of DEX on I Ca,L in differentiated NG108-15cells.Cells,bathed in normal Tyrode’s solution containing 1.8mM CaCl 2and 1m M tetrodotoxin,were held at 240mV and voltage pulses ranging from 240to +50mV in 10mV increments with a duration of 300ms were applied.In (A ),superimposed current traces shown in the upper part are control,and those in the lower part were recorded 2min after application of 10m M DEX.Voltage protocol is shown in the uppermost part.(B )Averaged I–V relationships of peak I Ca,L obtained under control or during exposure to 10m M DEX.Mean (SEM )(n =6–8).The I–V relationships of I Ca,L in the absence and presence of DEX are virtually superimposable.
Chen et al.
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(i.e.activation time course)was elevated in the presence
of this agent.At the beginning of the depolarizing stimuli,
d I /d t is proportional to th
e number o
f channels available
for activation.Our experimental results showed that the
values of d I /d t and t
act were signi?cantly altered during
exposure to DEX,suggesting that DEX reaches the block-
ing site only when the channel is in the open state.No
modi?cation of the steady-state inactivation of I K(DR)can
be seen in the presence of DEX.Thus,block by DEX of
I K(DR)presented here tends to be located at the open states
of the channel.It is also possible that DEX has a greater
af?nity for the open conformation of K DR channels than
the closed conformation even without producing a block at
the open states.However,it will remain to be determined
whether other types of K DR channels can be differentially subject to block by this drug or other structurally related
compounds.
We provide the direct evidence that DEX has a depress-
ant action on I K(DR)in differentiated NG108-15cells.The
half-blocking concentration of DEX required for inhibition
of I K(DR)with an IC 50value of 4.6m M appears to be of
the same order of magnitude as the concentration used
elicit outward K +currents in other types of neurones.910The concentration used in this study tends to be greater
than mean plasma concentration during sedation (0.9–2.3ng ml 21;4–10nM).22–24However,the concentration
immediately after a bolus of
injection with DEX can range
between 0.1and 1m M.22–24Individual patients can differ
physiologically owing to differences in regional blood ?ow or volume of distribution.2425Moreover,the I K(DR)and I Na in response to AP waveforms were more sensitive to block by DEX than those evoked by rectangular pulses.Control B A A P
D 90 (m
s
) 3 μM 10 μM m V a b c Fig 6Effect of DEX on APs in differentiated NG108-15cells.Cells were bathed in normal Tyrode’s solution containing 1.8mM CaCl 2.Patch
pipettes were ?lled with a K +-containing solution.Changes in membrane potential were measured under current-clamp con?guration.(A )Potential traces obtained in the absence (a)or presence of 3m M (b)or 10m M (c)DEX.(B )Summary of the data showing the effect of DEX on APD at 90%repolarization (APD 90).Each bar represents the mean (SEM )value (n =7).Statistical comparisons were performed by paired Student’s t -test (*P ,0.05vs control).a b Control 1 μM 3 μM
m V A Time (ms)ms 2015–1000–500
0a b p A p A Fig 7Inhibitory effects of DEX on AP waveform-induced currents in differentiated NG108-15cells.(A )Current traces obtained in the absence (a)or presence (b)of 1m M DEX.The upper part shows the AP waveform generated from an NG108-15cell.The inset indicates expanded time scale of current traces (dashed box).(B )Summary of the data showing inhibitory effect of 1and 3m M DEX on I Na (?lled box)and I K(DR)(open box)in response to AP waveforms.Each bar represents the mean (SEM )(n =6–9).Statistical comparisons were performed by paired Student’s t -test (*P ,0.05vs controls).
Dexmedetomidine inhibits neuronal ion currents
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The K DR channels may thus be an important target for the action of this agent.Both the alterations in the channel gating and the reduction of the currents caused by this agent are also likely to be clinically relevant,if similar results are found in intact neurones in vivo .To what extent block of I K(DR)presented here contribute to the unusual
subcortical form of DEX-induced sedation 3also remains to be further elucidated.Intracellular dialysis with 10m M DEX had little or no effects on I K(DR)or I Na in differentiated NG108-15cells.Although its detailed mechanisms are unclear,the site of DEX action could be localized mainly on the extracellular side of the channel molecule near the outer channel mouth.Moreover,previous studies showed that in hypo-thalamic paraventricular nucleus neurones,DEX (0.1–20m M)suppressed hyperpolarization-elicited inward current and activated G-proteins-coupled inwardly rectifying K +currents,and yohimbine antagonized DEX-induced effects.9However,in the present study,in cells treated with yohimbine or efaroxan,DEX-induced inhibition of I K(DR)was unaltered.Therefore,block by this agent of I K(DR)or I Na in differentiated NG108-15neuronal cells appears to be direct and is unlikely to be mediated through binding to a 2-adrenergic receptors.Previous reports at our laboratory demonstrated the ability of propofol to reduce the amplitude of I Ca,L in H9c2myoblasts.26However,in this study,little or no effects of DEX on I Ca,L was observed in differentiated NG108-15cells.The observations seem to be different from earlier studies showing the ability of this agent to modify the amplitude of I Ca,L in phaeochromocytoma cells treated with nerve growth factor.7This discrepancy is currently unclear;however,it could be due to the fact that there are different types of Ca 2+channel-forming subunits in different cell types.The Ca V 1.3(a 1D )Ca 2+channel-forming
subunit is predominantly expressed in NG108-15cells.
27It has been reported that K V 3.1,one of the Shaw -type
K +channels,is the major molecular component of I K(DR)
in differentiated NG108-15cells.12–14A partial block of the classical Hodgkin–Huxley-type K +current leads to the increased number of evoked APs,whereas a partial block of the slowly inactivating I K(DR)(e.g.K V 3.1-encoded current)can decrease the number of evoked APs.28Through an inhibition of I K(DR)presented here,DEX can depolarize the cell and exacerbate the inhibition of I Na to a greater extent,thereby diminishing its depressant action on I Na .Therefore,the block by DEX of I K(DR)at depolarizing potentials can delay repolarization,which could cause a reduction in neuronal excitability.Besides its action at a 2-adrenergic receptors,DEX exhibits some af?nity for imidazoline binding sites.29Previous studies in isolated portal vein cells have demon-strated that several agents containing an imidazoline moiety can induce the inhibition of I K(DR).30DEX was recently reported to increase the expression of phos-phorylated extracellular signal-regulated kinases via a mechanism linked to its binding to imidazoline I 1recep-tors.31It is thus possible that DEX exerts its inhibitory effects on I K(DR)by an interaction with an imidazoline binding site.It also remains to be clari?ed whether levo-medetomidine,an inactive isomer of DEX,22has any effect on I K(DR),although this agent showed little pharmacological action.C u r r e n t a m p l i t u d e (p A )A
Control DEX
Time (ms)
ms 0200–400mV 400Fig 8Effect of DEX on I K(DR)in isolated cerebellar granule cells.Cells were bathed in Ca 2+-free Tyrode’s solution that contained tetrodotoxin (1m M)and CdCl 2(0.5mM).(A )Superimposed current traces obtained in the absence (upper)and presence (lower)of 3m M DEX.The inset indicates the voltage protocol used.(B )Averaged I–V relationships of I K(DR)obtained in control or during the exposure to 3m M DEX.Mean (SEM )(n =7).Chen et al.
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In summary,the inhibitory effect of DEX on I K(DR)in NG108-15cells and in isolated cerebellar granule cells is not associated with binding to a 2-adrenergic receptors.Because of the importance of I K(DR)(i.e.K V 3.1-encoded current)in contributing to excitability and automaticity of neuronal cells,these effects shown in this study could provide novel insights into electrophysiological properties of DEX and other structurally related compounds.Funding This study was partly supported by a grant from Buddhist Dalin Tzu Chi General Hospital (DTCRD98-08),Chiayi County,Taiwan.The work in this laboratory was also sup-ported by grants from the National Science Council (NSC-95-2745B-002-MY2),and the Programme for Promoting Academic Excellence and Developing World Class Research Centers,Ministry of Education,Taiwan.References 1Scheinin H,Virtanen R,MacDonald E,Lammintausta R,Scheinin M.Medetomidine—a novel a 2-adrenoceptor agonist:a review of
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---------------------------------------------------------------范文最新推荐------------------------------------------------------ 学校学生请假条格式【通用】 学生请假的理由有很多种，下面是小编精心整理的学校学生请假条格式，希望能给大家带来帮助! 学校学生请假条格式一 尊敬的______老师： 您好! 您的学生________因______________________需请假__________学时，望老师批准。 (请假日期：__________年_____月_____日至__________年_____月_____日) 请假人：______________ _____________________学院 _______________________(班级) 联系电话__________________________________ __________年_____月_____日 班主任：(签字)________________________________ 学办：(签字、盖章)________________________________ 学院签字：签字________________________________ 备注：请用整张信纸，按照以上格式黑笔书写，一式二份，三天以上学院领导签字。 学校学生请假条格式二 1 / 15
张老师： 今天，我因感冒发烧，不能到校上课，请假一天，请予批准! 请假人： 日期 学校学生请假条格式三 尊敬的老师： 您好! 我系XX年级XX几班的XX同学。我一直学习拉丁舞x年了。我报名了在X天xx地方举行的拉丁舞比赛。因为明天晚上要进行最后的彩排，后天上午9点比赛。因此会印象上课。在此深感抱歉，需要向老师(学校)请假，时间是明天下午到后天中午。 望老师(学校)予以支持和谅解，给予批准，在此为谢! XXX XX年XX月XX日 学校学生请假条格式四 由于运动会，我系院有以下运动员要参与训练，故不能参与XX月XX号至XX月XX号晚自习，请谅解! 参与训练名单如下： XX级XXX班：姓名学号 姓名学号 姓名学号 姓名学号
【实用】学生推荐学生的推荐信范文集合8篇 学生推荐学生的推荐信篇1 尊敬的用人单位： xxx同学，现为xxxx高等专科学校英语系系英语教育专业应届专科毕业生，其具体情况是：性别：女民族：汉出生年月： xxxx.xx.xx 政治面貌：团员专业学制：三年培养方式：国家任务在校担任社会工作：学校社团联合委员会办公室主任在校曾获奖励：特长：看书、体育运动职业技能水平：国家计算机一级、普通话二级乙等、英语应用能力四级等职业技能培训，成绩合格。家庭地址： xx市xx县xx镇xx村在校通讯地址：xx市xx 区xx路x号联系电话：xxxxxxxxxxx 依据国家关于高等学校毕业生就业的有关规定，学校同意该生求职择业，现特向贵单位推荐。此致敬礼系主任签字：系公章：xxxx高等专科学校招生就业处(盖章) xxxx年xx月xx日学生推荐学生的推荐信篇2 尊敬的老师：您好！我们是****的家长，我们对贵校的教学条件和实验班的师资、办学成果仰慕已久。现在我们的孩子马上就要小学毕业，故而特向贵校发出申请，想进入贵校实验班学习，希望各位老师予以考虑，孩子和我们都如切的希望能够得到一个去贵校面试的机会。(客气的话，应该有一些，但不要太多罗嗦) 下面我向各位老师介绍一下孩子的情况： ****是北京市***小学的学生，从入学以来，一直是三好学生，孩子在各方面的学习成绩都非常突出，学校的课程就不用说了，全部是优。(简单描述、介绍) 另外孩子在课外的学习中也是非常出色，尤其是奥数的成绩：一直在仁华学校学习(如果有的就可以进行描述)，一直在学校的数学A班学习，业余时间还参加了一些比赛，比如在四、五年级的时候在“希望杯”中都取得过(成绩描述)，六年级的时候还参加了“迎春杯”。(这一段对小学阶段参加的所有的奥数比赛进行细致地描述)。孩子在文科方面的学习也是非常出色，在业余时间里学习了新概念、剑桥等英语，通过了***考试(比如剑桥三级、公共一级等等方面的成绩)。在语文的学习中也取得了非常好的成绩，在“春蕾杯”中也多次获奖。更重要的是这个孩子的表达能力非常突出，写作能力也很强。(这一段对小学阶段参加的英语、语文进行细致地描述)。更可贵的是
春风拂面 每每想起老师，仿佛总有一股春风从面前拂过。它那样温暖，那样和煦，像润物无声的细雨，慢慢地催开了我心底那美丽的花儿。 老师，您是否还记得那次午休?同学们都伏在课桌上睡觉，后来外面下起了雨，阵阵凉凉的风吹进教室，吹乱了您的头发，也吹乱了同学的衣裳。您正想起身做点什么，突然您好像想起了什么，又坐了下来——噢!只见您脱下了您的高跟鞋，轻轻地走到窗户边，悄悄地把每一扇窗户都关上了。啊!老师，您是怕吵醒了那些可爱的熟睡的孩子呀!老师，您知道吗?那一刻，我觉得自己就像是一个孩子，生活在母亲的怀抱。那一刻，我觉得您就像一 股春风，悄悄从我们身边吹过。 老师，您可曾想起那个炎热的下午?我们在楼梯口相遇，我道了一句“老师好”，您甜甜一笑，走过来，轻轻地拉了拉我的衣领：“热不热?”突然，您发现我的脖子上那些红肿的小疱，您关切地问：“呀!这是怎么回事，蚊子咬的吗?”我点了点头。没想到第二天早上，您就给我带来了驱蚊花露水。那一刻，我又惊讶又感动。望着同学们羡慕的眼光，我的心底仿佛拂过一缕春风，温暖而幸福。 老师，您是否记得那次晨读?同学们都在教室里认真地读书，忽然，我感觉有个身影从我身旁走过。一抬头，我才发现桌子上多了一瓶牛奶，上面还有几个有趣的字“喝了长高噢”。再朝那个身影望去——乌黑笔直的秀发飘在肩后，我知道，是老师您。 老师!您知道吗?在住校的那段时间，我时常会记起您，我时常会抱着那花露水瓶子睡觉，我时常会穿着您送我的带着香味的衣裳…… 一阵春风轻轻拂过，我仿佛又看到了您那熟悉的身影。 春风拂面 岁月是爱人的，每年，即使春已逝去，也会在某一个时候给人以春风拂面的感动。 我平时喜欢写作文，语文老师就鼓励我向报刊投稿。“我?能行吗?”看着老师坚定的眼睛，我下定了决心。但是一次又一次的石沉大海，我又开始灰心了。 “来，文章见报了……”声音温和，是语文老师。似乎早有预感，庆幸却又疑惑。我已忘了自己还死僵僵地坐在座位上。老师满脸笑容地离开了。“真没礼貌!”身旁的男生嘀咕道。这才醒悟：我，就是一个忽视了最简单的礼貌的人。 仿佛为我的坏心情应景一般，风儿大了，调皮地飞驰而过，掠走了我的微笑。上课后，老师就就一些难题向我们指点迷津。教材第110页……”黑板上显现出一行醒目的大字。还没等老师说完，我就心急火燎地开始复制克隆，笔走龙蛇。不料被老师撞见，批评了一句：“做题时要看清题目，再去对照答案……当时，真是无地自容，还是科代表呢!名不副实。这才明白：我，就是一个冒冒失失的人。 下课的时候，狂风骤起，刹那间将我无奈的寂寞卷入云层。学习上的退步，甚至让我怀疑自己就是一个超低智商的人。于是，一次次地摔跤、失落、放弃、流泪。感觉生活就是一座幽深的城堡，欲离去却始终找不着方向。可是，在晚饭时，当妈妈把熟悉的饭盒递到我手中，接着是匆忙的问候，我忘记了吃饭，那一刻，忽然感觉到如春风拂面，幸福无比。 我总是这样，预先准备了对待苦难的从容，却没学会从苦难中体验快活，总是注重自己的感受，却忽视了身边一直伴随提醒我的亲人朋友。同学的良言规劝是幸福，老师的悉心开导是幸福，亲人馈赠的欣悦是幸福……这样的幸福太多太多。 一路上，被人提醒，如沐春风。 [点评]这篇文章在选材时注重了“小处着眼”，写生活中时时处处有人提醒：忽视礼节，冒冒失失，忘记吃饭，这些琐碎的生活片段，写出了对生活深层次的感悟，紧扣“提醒”，揭示主题：原来，生活中有了提醒，是一种莫大的幸福。 春风拂面 春风，在我心目中是最纯洁、最高尚的。它从容淡定、缥缈虚无，同时又是世间自由不羁的精神所在，亦如那些从历史里缓缓走来的身影…· 那不羁的风，我想，是李白吧!他有"飞流直下三千尺，疑是银河落九天"的气魄，他有"仰天大笑出门去，我辈岂是蓬蒿人"的潇洒，他有"安能摧眉折腰事权贵，使我不得开心颜"
中学请假条范文3篇_请假条 阁巷中学学生出校门请假条(表一) 班级 姓名 事由及去向： 离校(班) 时间月日时分 大约所需 时间 家长 联系电话 申请人签名_______________ 年月日 (此表由请假学生本人填写，准假人员留下存档) ……………………………………………………………………………………………………
阁巷中学学生出校门证明(表二) 班级 姓名 事由及去向： 离校时间 月日时分 回校时间 (门卫填) 月日时分 门卫签名__________ 准假人员签名_______________ 年月日 (此表只能由准假人员填写，学生凭此条出校，回校时由门卫填好回校时间后留存) 阁巷中学学生出校门请假条 中学生请假条主要结构范文 中学生请假条主要结构范文 1.居中写标题请假条“请假条”，这是所有应用文的通用
要求，用来表明此文是用来请假的条子! 2.请假对象的称呼，要请假必须得到批准，这个地方往往是老师、领导等，这个地方要尊称喔! 3.请假原由，这个地方要实事求是，否则后果自负! 4.请假起止时间，这个非常重要，必须重点提出，明确。 5.祝颂语。祝福对方，这个是所有公文里表示对对方的友好。 6.请假人签名。你自己的签名，一般不用按手印，只需要签即可。 7.请假时间。当前你写请假条的时间。 高中学生请假条格式模板 请假条 尊敬的老师： 本人因需向您请假天(节) ，请假时间为：20 年月日午第节至20 年月日午第节。特此请假，恳请老师批准! 此致 敬礼! 请假人： 请假申请时间：20 年月日
本人联系电话： 家长电话： 班级：请假类别：□ 病假□ 事假(已请示班主任同意)班长证明签：班主任(科任教师)意见及签： 备注：学生办完事应及时回校，不得在外逗留，否则，将做严肃处理，学生离校期间一切安全事故自行负责。 中学生请假条的样本 请假条 尊敬的______老师： 我是_____________初\高______级_____班学生__________，因_____________________，特向您请假___________(多久)，请假时间为_______年____月_____日_________至__________。离校期间一切安全责任由我(学生本人)自负，请您准假! 教师意见： 请假人：___________ _______年____月_____日
小学语文《想象作文》教案设计之一 小学语文《想象作文》教案设计之一 一、教学目的 1．启发学生自由地想象，培养学生的创新思维能力。 2．指导学生有序地、重点突出地、主次分明地说和写。 3．培养学生热爱学校、热爱生活、热爱科学的思想感情。 二、教学重点 启迪学生展开大胆、丰富、新奇的想象，并指导学生有序地、主次分明地说和写。 三、课前准备 1．课前学生绘制自己心目中《未来的......》构想图。 2．制作多媒体课件。 四、教学时间 二课时（第二课时为写作及讲评） 五、教学过程 第一课时 （一）导入
1．谈话：(出示课件1后)小的时候，我就曾经幻想过，如果我能够像小鸟一样，有那样一对翅膀，那该多好啊！现在你们又有怎样的想象呢？（板书：想象） 2．结合学生回答表扬“你的想象真大胆！”.“你的想象真丰富！”.“你的想象真新奇！”（教师板书：大胆.丰富.新奇） 3．小结：希望同学们能把大胆.丰富.新奇的想象，在自己的作文中体现出来。（4分钟） （二）本次作文指导经过。 1.让我们乘上宇宙飞船，穿越时空隧道，去未来看一看吧！（出示课件2）（1分钟） 2.我们还在去未来的路上，但是伟大的科学家爱因斯坦曾经说过：“想象是一切创造之源。”（出示课件3）这节课让我们用想象创设一下未来吧！同学们，今天这节课，我们就来写一写未来的......（板书：未来的......）（出示课件4）（1分钟） 1．读一下课题，你觉得可以写什么？进行讨论。（3分钟） 提示：人物、事物、军事、科技、农业、环境、体育等等。 估计可能有的题目：《未来的我》、《未来的生日》、《未来的母校》、《未来的教师》、《未来的祖国》，以及《未来的地球》、《未来的汽车》、《未来的学校》。 明确：在现实生活的基础上，随着科技发展，将来可能实现的设想或可能拥有的事物才可写。 2．我们选好了要写的题目，那么怎么来写，具体写些什么呢？ 3．学习小组进行讨论，要求：
学生推荐学生的推荐信范文10篇 学生推荐学生的推荐信范文10篇 学生推荐学生的推荐信篇1尊敬的领导： 您好! 首先衷心感谢您在百忙之中浏览我的自我推荐信，为一位满腔热情的大学生开启一扇希望之门。 本人毕业于XX学校计算机网络专业。在三年的学习期间，系统学习了计算机网络专业相关的技能知识。通过三的年努力学习，自己在学习上取得了一定的成绩。并获得了英语二级证书、职业资格证书、高薪技能证和计算机等级证等多种技能证书，还熟练的掌握了网页设计方面软件的使用。 思想和精神的完善，才是人真正的完美。在完成学业和实践活动过程中，我不断地加强自己的思想道德修养，既要学会做事，又要学会做人，恪守“有所作为是人生的最高境界”的人生信条，积极奉献，乐于助人，多次参与社会捐赠和公益活动。生活上本人始终保持着艰苦朴素、勤俭节约的优良作风。在校期间，我积极的向党组织靠拢，慎重地向校党委递交了申请书，定时的向党汇报自己的思想情况。在党组织的温暖关怀和教育下，使我认识到入党的重要性，也使我的思想觉悟有了很大的提高。我尊敬老师，团结同学，关心热爱班集体，有着强烈的集体责任感。
作为职业技术学校的学生，掌握扎实的专业技能是我们在竞争中致胜的法宝。因此，我随时注意到理论联系实际，刻苦、投入，认真学好每一门课程。增强自己的实际操作能力。在学习专业知识和拓展个人兴趣的同时，强烈的集体荣誉感和奉献激情又使我积极、热情、务实地投入到一些有益的社会活动中。在假期中，我认真参加了社会实践，使我学到了在书本上学不到的知识，尽管时间很短，但体会颇深，无论是在业务能力，还是社交能力，都有一定的提高，具备了一定的工作经验。 虽然我刚从学校毕业，工作经验有限。但是，在这次应征之前，我就对自己进行了中肯的评估，我觉得以我有较扎实的专业知识与较强的敬业精神，实践经历，我相信自己适合从事网吧管理、组网、网页设计、图形图像处理等相关工作。请您相信我，给我一个发展的机会，我会以一颗真诚善良的心、饱满的工作热情、勤奋务实的工作作风、快速高效的工作效率回报贵单位。 剑鸣匣中，期之以声。非常盼望能与您进一步面谈。若承蒙赏识，请与我联系，期盼您的佳音。 最后，衷心祝愿贵单位事业发达、蒸蒸日上! 推荐人：XXXXXXX年XX月XX日学生推荐学生的推荐信篇2 您好!很荣幸能向你推荐我的学生yjby,yjby同学是一名非常优秀的学生，无论是学习、品德、还是能力都非常出色。 学习刻苦认真，上课专心听讲、勤作笔记，最难得的是他有自己的学习方法与学习理念，他了解自己的长处与短处，能根据自己的个
常用学生请假条格式范文_请假条 (二)学生请假条 尊敬的______老师： 我因____________(请假缘由)，无法在准时到校上课。特此向您请假____________(请假时间)，望您批准，谢谢您的理解和帮助。 此致敬礼! 学生： 年月日 (三)学生请假条 尊敬的______老师： 我是_____________初\高______级_____班学生__________，因_____________________，特向您请假___________(多久)，请假时间为_______年____月_____日_________至__________。离校期间一切安全责任由我(学生本人)自负，请您准假! 教师意见：______________ 请假人：___________ _______年____月_____日 (四)学生请假条 我是_______级本科生_______(姓名)，学号_______，因_______(事由)需请假，离校时间_______年_____月_____日_____点_____分，预计返校时间_____ 年_____ 月_____日_____ 点，离校期间联系方式_______________ 。本人已接受辅导员的安全和纪律教育，保证按时返校，请假外出期间个人一切安全责任由自己负责。 __________ 请假人： 时间： 请假条存根 我是_______级本科生_______________ (姓名)，学号__________ ，因_________________________ (事由)需请假，离校时间__________年_____月_____日_____点_____分，预计返校时间_____ 年_____ 月_____日_____ 点，离校期间联系方式_______________ 。本人已接受辅导员的安全和纪律教育，保证按时返校，请假外出期间个人一切安全责任由自己负责。 __________ 请假人： 时间： 附：学校学生请假制度 一、请假条由政教处统一发放到班主任处，请假均需要先到班主任处领取请假条，填写完毕，经班主任批准，方可请假。 二、因故不能自己来请假或来不及请假的，回校第一天马上到班主任处签字补假。 三、学生事假应持有家长证明书，病假应持医疗单位证明。一天以内由班主任审批，叁天内由政教处审批，叁天以上由校长室审批。 四、各班考勤员必须记录每天上课、自修和其他集体活动的出勤情况。周五下午将考勤表送交政教处，周一早上领取。
三年级下册语文第五单元作文《奇妙的想象》写作指导 一、审题 写一个想象故事。展示自己的奇妙想象，创造出属于自己的想象世界。 二、选材 写想象的故事。，而不是现实生活中的事，如矮人国的故事、大熊开面馆的故事、小狗变巨人、我有魔法了……只要是你能想到的故事都可以。 三、构思 我们以《最好玩的国王》为例进行构思，简要列出习作提纲。 开头：交代国王的爱好：微服私访。(略) 中间：微服私访时发现了一本畅销书，他大受启发，自己也写了一本书，后来这本书也非常畅销。(详) 结尾：交代畅销的原因：这本书太无聊，人们买来治疗失眠。(略) 四、表达 ①为习作起一个有趣的名字，如《播种女巫》：②大胆想象，让想象的内容神奇、有趣；③记得上自己平时积累的一些好词佳句哟！
写作素材 一、题目 《瞌睡虫多多》《小豆苗历险记》《白雪公主后传》《月亮又瘦了》 二、好词 无影无踪大摇大摆活灵活现转瞬即逝 神秘莫测窃窃私语一模一样大吃一惊 远走高飞 三、好句 开头 1.晚上，一道金光闪过，我突然发现睡在身边的妹妹变成了一个巨大的金蛋。我急坏了，怎么才能把妹妹救出来呢?把蛋砸破，可能会伤到里面的妹妹。把蛋刹开妹妹会不会变成蛋清流出来呢?我想了又想，最后决定把妹妹从蛋里孵 出来。 2.在离天河不远的地方，有三颗小星星。说来也巧，这三颗小星星是同年、同月、同日、同时生的，可它们彼此都不一样：一颗是蓝的，一颗是红的，第三颗最小，似乎没有什么颜色，只有一点儿微弱得可怜的光。 结尾 1.从此，绿森林里多了一个永久性的居民，绿森林的动物们多了一个永远的朋 友，绿森林的故事里多了一份传奇。 2.大力士风孩子回来了，呼呼吹了几口气，白烟被吹跑了，烟筒和房子被吹倒了那几个黑衣人被吹到了森林外。大树们开心地笑了。
三好学生推荐信范文 三好学生推荐信范文1 敬爱的领导： xx卫校学生xxx，经老师和同学一致评选，决定推荐该生参加校＂x级三好学生＂的联选 活动。 xxx性别：女；出生于1990年3月11日；政治面貌：团员。该生自20xx年进入卫校以来，一直担任班级的学习委员。在学习上她积极要求进步，上进心强，各方面严格要求自己，成绩优异，受到老师们的一致好评。 在老师的辛勤培育和教导下，在思想上，该生积极参加政治学习，热爱祖国，热爱人民，热爱党，热爱领袖，坚持拥护社会主义制度，关心国家大事，同时参加了业余党校，积极主动的向党组织靠拢。 升旗时她总是提前到达操场，庄严肃穆，等待着升旗仪式的开始。国歌响起，肃然起敬， 用一颗炽热的爱国心默默的唱想国歌，目光随着五星红旗冉冉升起，升旗仪式结束，自觉拣起周边的垃圾，她热切期待中华民族能尽快以一个强大的社会主义国家立于世界民族之林。 该生集体荣誉感强，在任学习委员期间，积极主动的做好本职工作，利用课余时间辅导一些后进同学，帮助她们进步，尊敬师长关心同学，先人后己，积极向任课老师班主任反映 同学们的愿望和意见，敢于当面向同学提出善意的批评意见。 该生不仅思想上要求进步，在学习方面，更是一位勤奋刻苦，勇于探索的好学生。她学习态度端正，目标明确，刻苦认真，主动好学，成绩优秀，成绩始终在班级名列前茅。曾经多次获得＂三好学生＂和奖学金。 该生有良好的学习习惯，如课前预习，上课认真听讲，积极回答问题，课后认真完成作业并复习等。她热爱所学专业，为了提高综合能力，还报考了英语PET等级考试。不断的 自我完善，是为了使自己努力成为一名复合型的医护人才。勇于挑战自我，敢于面对挫折，也使自己有了一颗坚强的心。 该生平时经常请教老师同学学习方面的问题，注意摸索学习方法，积极配合老师共同搞好教学活动，使班级学习气氛不断上升，同时也增强了班级凝聚力。 她自觉遵守学校和宿舍的各项规章制度，处处以班干部标准要求自己，以身作责，树立带头作用，注意个人卫生及环境卫生，在＂创卫＂活动中，不怕脏，不怕累。她尊敬老师团结同学，好结交朋友，与周边的人和睦相处，待人真诚。
关于春风的作文（6篇） 【第1篇】关于春风的作文：春风赞 所谓的春风，如此温柔。瞧！春风轻吻着柳枝，柳枝有节奏地摇摆着，摆动着它那细腻的腰姿，微微地吹皱了水面，偷偷地传送着花香。如此温柔、如此温柔，就像万物的母亲，无微不至地亲切体贴着万物，让万物生机勃勃地活动着。微风吹拂着千万条嫩黄色的柳枝，为它们换上了新衣裳；迎春话、牡丹花……春风吹拂着那娇媚的花儿，人们不由得分外爱惜！ 一切万物只因它！ 它就像一位慈祥而细心的“母亲”，她辛勤地培育着“儿女”，用她那甜美的乳汁来赋予营养给儿女，为的是什么呢？她为的是给儿女更好的东西、更好的生活和更好的体魄。儿女长大了，母亲给了他们最好的教育和贴心的爱护。如今儿女已经可以挣脱开母亲的怀抱，展翅飞翔，翱翔在天空中，那这些功劳归功于谁呢？一切都是母亲在儿女的背后默默支持的结果。 春风仿佛是一种生命的动力，它可以唤醒万物，也可以成为人的力量。春风扑面而来，使我想起了“一年之季在于春”春给人带来了新的一年，新的希望，新的人生目标……一阵春风吹来，我的头脑顿时清醒了，明白了人不仅要学，还要懂得运用。用春风来唤醒自己心中的渴望，让它告诉自己应该努力发奋，为自己的渴望而发奋实现
这美好的愿望。所以我们要珍惜这种源之动力之风。 春风如此温柔、如此细腻，怎能不让人心动去珍惜呢？让我们一起珍惜这股动力之风吧！ 【第2篇】关于春风的作文：春风拂面 春天来了，太阳公公擦擦自己的眼，戴上眼镜，俯瞰世界，感叹：“这会是美好的一天。”风姑娘轻悄悄地来到了人间，用手轻抚柳树姑娘的头发，柳树姑娘醒来了，才发现这时的头发被某人梳理了一下，风姑娘摸着小草的头，轻声说：“该起床了！”这时，小草睡眼惺忪的睁开了眼睛，伸了伸懒腰。不一会儿，世间万物都从睡梦中醒来了。 她在床上熟睡，“起来，快起来！”闹钟好不耐烦的叫着，她醒了来“哎！好梦就这样被破坏了！”迅速的穿好衣服，急匆匆地走到了学校。她从书包里拿出书，大声朗读书中的内容，读着读着，就觉得有点困，本想伏在桌上休息的，她看到成绩比较好的来到了教室，她于是从书包里来翻到有问题的一页，走到他们面前寻求解题思路，问题进一步得到解决。此时春风拂面，振作了他疲惫的精神。 他和同学坐在一起，它却只能沉默过眼地陪伴这同学，他深感歉疚，同学忍不住要和他讲话，她在旁边认真地听，认真的回答他们提出问题，把心中的烦恼全部说出来了。心中舒服了好一阵子。这时春风拂面，排除了她心中的烦恼，则多了一份快乐。 从窗外望——处处都充满绿色，五彩缤纷的花点缀着绿，小鸟
学校请假条范文 请假条 敬爱的老师: 您好!由于我晚上要在公司上班,晚上不能去上课了,请您批准! 请假人:某某某 时间 请假条 敬爱的**老师: 我是**学院**级学生,学号:******,因**************将于****年**月**日至****年**月**日外出,****年**月**日**点返回学校,目的地*******,外出期间联系方式********,在外出期间自身人身财产安全由本人负责,我将注意安全,按时返校. 学生:*** ****年**月**日 尊敬的老师您好: 我是xx班的学生,平时也是按时的遵守学校的各项规定，从不敢逾越。然而，现在我却不得不向您请假。因为我哥要结婚。结婚是人生的一件大事。我不想让哥哥和我留夏什么遗憾。而且，父母，亲人，和哥哥都希望我能出席婚礼。于情于理，身为兄弟的我要出席哥哥的婚礼。在此，我诚恳的期望老师您能批准我的请假要求。向您保证，我会在规定的时间内赶回学校的。 尊敬的学校领导(或x校长): 您好 我将于近日结婚,婚期定在*月*号.是老人家定的.我也借此机会向您报告.因为最近比较忙,结婚的很多事情都没有怎么准备,双方父母催得特别紧,几次打电话要我赶紧请假去办.要我*月*日--*日务必去做必要的准备工作. 现在正置期末,学校和班里的工作又比较繁忙,真是不好意思向您说请假的事.万望您海涵准假. 谢谢
请假人 xxx 请假条 尊敬的老师： 您好!我是06级电子商务专业直属班的学生，因为，需要请假(时间)从到，去往地点，请假期间有效联系方式：。 本人保证往返途中的个人人身和财产安全，在不耽误学习课程和任何集体活动的前提下，恳请您批准，谢谢! 班长(副班长)意见: 班主任意见： 本人签名： 日期： dear mr. liu, i’m li jun’s mother. i’m writing to ask for permission for li jun’s absence. the fact is that he has to stay at home to take care of my mother who had a serious fall from upstairs and got her right leg broken last week. i’m sure he will be back in three days when my husband returns from a meeting in beijing. thank you. sincerely, li yihua 请假条 敬爱的老师: 您好!由于我晚上要在公司上班,晚上不能去上课了,请您批准! 请假人:某某某 时间 请假条 敬爱的**老师:
小学语文想象类作文的构思技巧整理 给文字插上想象的翅膀，想象类作文的构思技巧整理！ 学生在作文时，往往觉得没有合适的素材可写，或是不知从何想象。其实呢，不是生活中没有作文素材，而是学生缺少善于捕捉作文素材的能力。连素材都有限，自然就很难展开想象了。因此，培养学生的观察生活的能力，养成留心观察周围事物的习惯显得十分重要。 01 怎样指导孩子观察呢？ 1．观察周围尽可能看到的所有事物，捕捉典型材料。 孩子的视线往往局限于一个小圈子，觉得一些司空见惯的小事没什么可写的。其实，平常的小事也可写出新意来。要选择最佳的观察对象，安排合理的观察顺序，认真观察。2．动用多种感官，丰富写作素材。 心理学认为，观察是思维的知觉，没有思维的观察是肤浅的，不是真正的观察。观察不仅仅是看，要动用耳、口、鼻、手、脑等感官去多方面地感知或判断，获得真实、全面、深刻的印象，为作文提供丰厚的材料。3．填写观察记录，养成观察习惯。 观察不应只是一次作文之前的例行公事。还应填写观察记录（观察顺序、观察方法）。 02 如何构思 以《卖火柴的小女孩》为例题，小女孩五次擦燃火柴所看到的奇异景象是作者的想象。这些想象奇特而大胆，而读者仍然觉得合情合理。
为什么呢？因为作者亲眼目睹了穷苦孩子的悲惨遭遇，深深地理解他们的内心需求。在文章中，想象与现实有着相似的地方，那就是穷孩子对幸福生活的渴望。 作者想象小女孩在神志不清时见到了温暖的火炉，喷香的烤鹅，美丽的圣诞树，慈祥的奶奶并和奶奶一起飞走，就显得自然而合理了。 无论写哪类想象作文，我们都必须做到以现实生活为基础，想象要合理、丰富，表达要真实、具体。 03 以现实生活为基础 现实生活是我们想象的源泉，离开了现实生活，想象就如同空中楼阁，成为无本之木、无源之水，变成空想或幻想。 所以，写想象作文必须勤于观察，丰富自己的生活，积极思考，驰骋想象，创新思维，这样才能引发你进行写作的灵感，进而写出优秀的想象作文。 04 怎样做到想象合理、丰富呢 1．再现 侧重于写景状物或叙事的想象作文，可以搜寻脑海中对相关事物的印象，加以再现。2．移植 有时候，想象可以进行嫁接、移植，把优美的景色移为一处，或把有趣的现象归为一物，或把美好的品质浓缩在一人之身。即，学生可以按自己的意愿中的特定形象，结合生活实际，进行移植想象。只有善于把想象与现实生活中的事实联系起来，巧妙地设计人物之间的关系，才能使文章生动有趣。3．幻想
学生推荐学生的推荐信范文9篇 学生推荐学生的推荐信范文9篇 尊敬的领导： 非常感谢您能在百忙之中抽出时间阅读本人的自荐信。 我叫XXX，是XXX学院公共艺术专业的一名即将毕业的大学生。多年扎实的学习让我具备了夯实的基础知识和基本能力。 四年的大学生活又让我系统的掌握了专业知识，在团队管理、市场策划、场所管控、服务管理及标准化流程控制等领域有一定的理论和实践基础;熟悉涉外工作常用礼仪;具备较好的英语听、说、读、写、译能力，以及韩语的口语交流和阅读能力;能熟练应用计算机办公。 同时，我利用课余时间广泛地涉猎了大量书籍，不但充实了自己，也培养了自己多方面的技能。更重要的是，严谨的学风和端正的学习态度塑造了我勤勉、朴实、稳重、创新的性格特点。 生活就好像是打一场扑克牌。有的人天生就握有一副好牌，有的人天生就握有一副烂牌。但是不管怎样，所幸的是，你还可以选择
打法，或者还可以选择搭档。而生活与打扑克牌不一样的是，一旦打出，就无法在收回，所以，每一步，都得三思而行。 我想我拥有一副不算差的妙牌。我生在鱼米之香的岳阳，“先忧后乐，团结求索”的岳阳精神一直激励着我奋发向上。我喜欢那种与人合作共同进步的感觉，以及观察人们各种各样的反映，去猜测他们的心理。我总在想人类是伟大的，发明出扑克牌这种游戏，方寸之间便尽显一个人的观察力，灵敏度以及与人合作的能力。 拥有一副好牌并没有决胜的把握，如果可以得到贵公司的提拔与合作，我想，我人生的这副妙牌可以打得更好。若能给我一个面谈的机会，我将倍感荣幸。恭候您佳音。 随信附上我的个人，期待与您的面谈。祝您身体健康，工作愉快!愿贵公司事业蒸蒸日上! 推荐人：XXX XXXX年XX月XX日 福州市金山小学学生，经老师和同学一致评选，决定推荐该生参加校“区级三好学生“的竞选活动。
春风送暖，如丝般的触感滑过脸际，送来温暖的气息。像圣洁的天使飘落的羽毛，又似冬日的火光映照着脸颊，勾起心底潜藏着的那暖暖的记忆。 “怦”，好险，好险。将将赶上这班车，不然，可又得等上半小时呢! “呼”，长舒一口气，抓好扶手。提着袋子，心头嘟囔：大夏天的还得去给表弟送书，什么世道，补课竟然都不带书，学的好才怪!心里愤愤的咒骂着。 “喂，我说这个女生，不想买票哟!”售票员不耐的声音总算唤回了我的神思。吐吐舌头，开始找钱包、掏钱、买票。等等!我钱包呢?糟了，莫不是跑得急忘在家里了?! 天哪，别开玩笑了。不过很可惜，上帝爷爷今天似乎睡觉去了，我全身上下摸不出一毛钱。 售票员看着我着急的样子冷笑着：“你这样的学生我见多了，什么‘钱包没带’‘钱掉了’的，我听得多了。小小年纪什么不学，学人家坐霸王车，害不害羞哟。撒起慌来脸都不红，羞不羞!” 我长这么大，什么时候被这样当众骂过。委屈的泪水一下子涌上了眼眶：“阿姨，对不起，我下车总行了吧。” “哟，装撒。现在的小孩哟，太会演了，怕是都已经到了要去的地方了吧。” 我咬着唇，拼命忍住眼里酸涩的泪水，自知理亏，也没办法反驳。 “阿姨，她是个女生，不过忘了带钱嘛，谁不没有点难处。你话也不能这样说啊。不就一块五嘛，我帮她买了。” 闻言侧头，身边是个和我差不多大的男孩儿。看着我，他轻轻眨了眨眼。清澈的目光既像关心，又像安慰，却更像春风拂过面庞，在炎炎夏日里带来阵阵温暖的清凉。眼里充盈的泪水，在此时，落了。 “谢谢，你叫什么名字。”我低低道着谢。 “呀，我叫什么呢?嗯，说‘雷锋’太老土了。有了!”他故意顿了顿，眼里满是狡黠，“我叫‘春风’。呵呵……” 春日，细雨蒙蒙。我望着窗外如丝般的雨，发着呆。忽的，我的童年记忆像一缕春风拂面而来，将我带回童年时代……
小学语文教学论文：想象作文教学浅谈 作文是语文教学的重点，也是难点，而想像作文更是难中之难，小学生大都有“恐作症”，老师也常常为此头疼不已。那么怎样才能让学生在想象作文中有内容可写，有话可说呢？我认为可以从以下几方面训练。 一、观察现实生活，激发相关想象。 想像离不开现实，离开现实的想象是空洞的，无论哪一类想象作文都脱离不了现实生活。例如童话式想象作文，它是根据小学生喜爱动物的特点，用动物代替人类的形象来表达他们对世界的认识，在想像力作用下的动物附上了人的动作、语言、神态和思维。这类作文实际上是对现实的再现。 如想像作文“未来的×××”，这一类写未来生活的想象作文对学生而言有难度。未来是什么样的，学生除了接触到一些科幻片、科幻小说以外，其他的十分抽象，不知如何写。教师可引导学生仔细观察现实生活，展开想像的翅膀。例如现在的房屋，一旦完工，它便固定下来。如果让学生大但想象，让未来的建筑由一个个组装件构成，根据不同的需要进行不同的组合，这样既适合不同人的需求，又便于搬迁、移动，还可以维修，那该多好。又如当看到学校操场只有一处，空间过于狭小时，可以引导学生想象地下或空中操场，用电梯或升降机来回启用……这些现实中人们追求的更加便捷、完美的东西，都可以大胆想象它的样子、形状、功能。如果激发了学生想象的火花，那么展现在学生面前的空间不知有多大！ 二、结合课文内容，进行再造想象。
课文是学生学习文化知识的重要材料，也是学生写作的典型范例。教师可充分利用课文资源，结合课文内容，让学生练习改写、续写、扩写等想象性作文，是一种行之有效的再造想象途径，能有效提高学生的想像能力。 例如《凡卡》一文，当凡卡满怀希望地把信寄出去后，爷爷能收到吗？爷爷在乡下会怎样想念凡卡呢？小凡卡后来的命运又会如何呢？让学生大胆去想象，续写出符合事情发展的故事，这样既加深了对课文内容的理解，又激活了学生想象的火花。 另外，还可以根据文中的插图进行补充或扩写。如《我的战友邱少云》一文在的插图，邱少云被烈火烧身时的巨大痛苦，是通过作者的心理活动侧面描写的，那么邱少云的心理感受会怎样呢？可引导学生观察他的神态、动作进行想象。 三、填补一些空白，设置整体形象。 在教学中选取一些相关的事物或词语，让学生进行整合，填补其中的空白，也是提高学生想象能力的重要手段。例如：画下几种不同的小动物，让学生按照自己的思维说出它们之间的关系，并想象出这些小动物之间会发生什么样的故事，然后进行口述表演，这样激起学生的童趣，他们的想象力就会更活跃。或者随便写下几个词语，让学生编上一段故事，用上这几个词语。这类填空白的训练，可以让学生的想象能力得到逐步提高。坚持长期训练，会收到意想不到的效果。 总之，学生作文能力的提高与教师的训练密不可分。我们应该在平时的作文教学中善动脑子，力求科学、有效，为学生作文插上想像的翅膀，让他们飞得更高、更远。
【必备】学生推荐学生的推荐信范文10篇 学生推荐学生的推荐信范文10篇 学生推荐学生的推荐信篇1尊敬的领导： 我是XX师范学校的一名毕业生，怀着对贵校的尊重与向往，我真挚地写了这封推荐信，向您展示一个完全真实的我，希望贵校能接纳我成为其中的一员。 首先感谢您在百忙之中浏览我的推荐信。 从小我就十分崇拜教师这一职业，随着年龄的增长、认识的提高，我更萌发了要做一名优秀的人民教师的愿望。经历了三年的学校生活，面对新的机遇和挑战，我更坚定了“自信、自强、勤奋、谦虚的人生信条。 我十分珍惜在校的学习时间，不断从各方面完善自己，每个学期都以较好的成绩完成规定学科的学习，同时也具备了一定的语言听、说、读写的能力，良好的教师素质，具有良好的语音面貌，自然、大方的教态，并在教学中善于创新，在课余时间我阅读了大量的书籍，对专业课的一些练习,我相信皇天不负有心人，只要自己努力了，就一定会有收获！ 21世纪的中国，竞争越来越激烈，对大批优秀人才的需要，是教师面临严峻的考验，作为一名有志的年轻人，我希望自己能成为教师战线上的新生活，更愿意在教育领域奉献一切“海阔凭鱼跃，天高
任鸟飞”，我相信，在老一辈教师的鼓励和帮助下，在自己的勤奋和努力下，也许我不一定会成为最好的，但我一定会是最努力的。 虽然我们未曾谋面，但请您相信，您的选择不会错，希望贵校能给我一次展现自我的机会，能让我成为贵校的一员。 推荐人：XXX XXXX年XX月XX日 学生推荐学生的推荐信篇2小学校长： 本人乃xx之家长。小女将於本年九月入读小学一年级。故现致函校长大人，恳请能给与小女面试的机会。我们深切希望小女有机会接受贵校的优质教育，成为贵校的一份子，渡过一个快乐的校园生活。 素闻贵校校风淳朴，办学严谨，怀作育英才之抱负，致力推动德智体群四育，学生表现出类拔萃，在社会及学界备受称誉，本人十分钦佩。所以一直对贵校之办学方针推崇备至，既著重学生的学业，又兼顾学生在课餘的发展，对德育培训亦重视有加。校长阁下与教职员工对教育事业俱有满腔热诚，作育英材，实為社会之幸。小女有幸获阁下惜才，到贵校接受教育，这对小女之成长实在有莫大益处。 小女资质实属不差，劝奋主动，若能获得校长及贵校老师启蒙，定必能造出显著成就。為了能成功入读贵校，小女幼稚园时就做好各种准备，参加过各类型的课外兴趣班和学前辅导课程，得以增进知识，培养自信及合群性格。小女聪敏好学，对语言、艺术尤具天分，学业成绩一直名列前茅。另一方面，小女亦属生性活泼的孩子，热爱舞蹈及钢琴，曾多次出外参与表演，在课外活动方面亦参加了英语唱游及
【篇一】一缕春风拂面来初三作文800字 无论冬天怎样漫长，春天就如同樱花般总会熬过严冬，以最美的姿态绽放于枝头，与你相见。——题记 20XX年的冬天似乎格外漫长，一场突如其来的新冠肺炎疫情袭卷神州大地。原本热热闹闹的新年，突然变得冷冷清清，和煦的春风也被阻隔在口罩之外。 出于安全考虑，人与人之间时刻注意保持安全距离，每个人的微笑也被隐藏在口罩之中。有一天上完网课，有些疲惫的我抬头看向窗外，突然发现门前的那棵树居然长出了嫩芽。之前因为功课太繁忙，每天早出晚归，披星戴月，所以从未注意到窗前的那棵树。今年春天延迟开学，我在家里上网课，所以有幸能见证它的生长。 那些刚刚长出的幼小嫩叶簇拥在一起，就像一朵小小的绿色荷花。那绿就像被雨水冲洗过一般，即使身在火热的夏天，也能让你的心底泛起一阵清凉。生命有时很脆弱，也许一场大雨就能把这些嫩叶摧残，可生命又如此顽强，即使被暴雨摧残，它们依旧能够长出新芽，继续生长。我们人类又何尝不是这样呢? 也许无情的病毒会夺走我们的生命，但是我们有能力、有信心从死神手里抢回。在这场人与病毒的战争中，我们看不到硝烟四起，但每天都有生死离别，阴阳两隔。疫情发生以来，每个人都在全力为抗疫作贡献。你看，爱与希望总比死亡与病毒蔓延得更快，这就是生命的张力与尊严。回顾历史，人类经受过很多苦难，在苦难面前，生命是何等渺小，但我们从不放弃活下去的希望。即使在苦难中，我们也艰难地摸索前行，去等待属于我们的春天，去感受那春风拂面的温柔。 这个春天，即使我们遭受过挫折，但生命却不会因为这些挫折而停滞，相反，它会拼命生长，在苦难中开花、结果。我想每一个熬过冬天的种子都有一个春天的梦想。让我们再等等，等到这个春天真正的到来，等到所有的花儿都开放，等到看樱花的人比樱花还要多，等到和煦的春风又再次抚摸脸颊。我们一定会摘下口罩，微笑问好。 【篇二】一缕春风拂面来初三作文800字 春风拂面，在其他任何季节，也会有一番如沐春风的舒畅与感动。 冬，一个寒冷的冬日，呼呼的寒风猛烈地刮着，呵气成冰的天气让我倍感不适，我因病体育课时在班中休息，听着外面强烈的风声，望着自己已冻得通红甚至有些僵硬的手，不禁一阵猛搓。这是，老师轻轻推开了门走了进来，端来一杯热水，关切的问道：“感觉好些了吗?喝点水，暖暖身子，如果不舒服直接去办公室打电话啊，不用找我。”我点点头，喝着水，感到无比的暖意，在这寒冬，我有一份感动，如同春风拂面。 不仅是在冬日，在夏日，也会有春风拂面的感觉。
学校学生请假条范文3篇 学校学生请假条范文一： 尊敬的______老师： 我是_____________小\初\高______级_____班学生__________，因 _____________________，特向您请假___________多久，请假时间为_______年____月 _____日_________至__________。离校期间一切安全责任由我学生本人自负，请您准假! 此致 敬礼! 请假人：xuexila 2021年X月X日 学校学生请假条范文二： 本人系 ____________级____________ 专业 ____________班学生，因____________ 原因请假 ____________天，前往，请予批准。 本人住在 ____________号____________ 宿舍，手机：____________ 宿舍电话：____________ 本人家庭所在地为____________家庭电话：____________ ，家长手机： ____________ 目的地详细地址：____________ 目的地电话：____________ ， 负责人手机：____________ 离校时间：年月日：交通工具及车次：返校时间：年月日：交通工具及车次： 是否批准辅导员签字是否批准学院负责人签字是否批准学校签字 注：1、外出期间一切事宜，责任自负。 2、此表一式二联，由班长、学院保留。 3、回校后本人去学院销假。逾期销假按学校学院相关规定处理。 此致
敬礼! 请假人：xuexila 2021年X月X日 学校学生请假条范文三： 尊敬的老师： 我因____________ ，不能按时上课，特向您请假。请假时间为年月日——年月日，望您批准! 学生：家长姓名：班级：家长电话： 学号：注：学生请假3天以上或者需暂时离学生联系电话：开学校的必须填写家长联系方式 此致 敬礼! 请假人：xuexila 2021年X月X日 感谢您的阅读，祝您生活愉快。