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1.
Voltage-dependent block of cardiac inward-rectifying potassium current by monovalent cations 总被引:6,自引:0,他引:6
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The inward-rectifying K+ current (IK1) in cat ventricular myocytes, like inward-rectifying K+ currents in many other preparations, exhibited a negative slope conductance region at hyperpolarized membrane potentials that was time-dependent. This was evident as an inactivation of inward current elicited by hyperpolarizing voltage-clamp pulses resulting in a negative slope region of the steady-state current-voltage relationship at potentials negative to -140 mV. Removing extracellular Na+ prevented the development of the negative slope in this voltage region, suggesting that Na+ can block IK1 channels in a time- and voltage-dependent manner. The time and voltage dependence of Cs+-induced block of IK1 was also examined. Cs+ blocked inward current in a manner similar to that of Na+, but the former was much more potent. The fraction of current blocked by Cs+ in the presence of Na+ was reduced in a time- and voltage-dependent manner, which suggested that these blocking ions compete for a common or at least similar site of action. In the absence of Na+, inactivation of IK1 could also be induced by both Cs+ and Li+. However, Li+ was less potent than Na+ in this respect. Calculation of the voltage sensitivity of current block by each of these ions suggests that the mechanism of block by each is similar. 相似文献
2.
In the marine hypotrichous ciliate Euplotes vannus, the transient K+ outward current, IK fast, was studied by use of a single-microelectrode voltage-clamp equipment. Activation and inactivation kinetics, and steady-state inactivation are comparable to the properties of A-currents. Not typical for this type of current is its insensitivity to either 4-AP or 3,4-AP and its Ca2+ dependence which was derived from its inhibition by either extracellular Cd2+, La3+, D-600, or by intracellular BAPTA. Actual amplitudes of IK fast were obtained from a composite current, by subtraction of early parts of a slowly activating K+ current, IK slow, and of the early, transient Ca2+ inward current, ICa fast, that is typical for ciliates. IK fast counteracts ICa fast during the first milliseconds after onset of depolarization such that the composite current is purely outward directed. 相似文献
3.
Bru-Mercier G Deroubaix E Rousseau D Coulombe A Renaud JF 《American journal of physiology. Heart and circulatory physiology》2002,282(4):H1237-H1247
The effect of catecholamine depletion (induced by prior treatment with reserpine) was studied in Wistar rat ventricular myocytes using whole cell voltage-clamp methods. Two calcium-independent outward currents, the transient outward potassium current (I(to)) and the sustained outward potassium current (I(sus)), were measured. Reserpine treatment decreased tissue norepinephrine content by 97%. Action potential duration in the isolated perfused heart was significantly increased in reserpine-treated hearts. In isolated ventricular myocytes, I(to) density was decreased by 49% in reserpine-treated rats. This treatment had no effect on I(sus). The I(to) steady-state inactivation-voltage relationship and recovery from inactivation remained unchanged, whereas the conductance-voltage activation curve for reserpine-treated rats was significantly shifted (6.7 mV) toward negative potentials. The incubation of myocytes with 10 microM norepinephrine for 7-10 h restored I(to), an effect that was abolished by the presence of actinomycin D. Norepinephrine (0.5 microM) had no effect on I(to). However, in the presence of both 0.5 microM norepinephrine and neuropeptide Y (0.1 microM), I(to) density was restored to its control value. These results suggest that the sympathetic nervous system is involved in I(to) regulation. Sympathetic norepinephrine depletion decreased the number of functional channels via an effect on the alpha-adrenergic cascade and norepinephrine is able to restore expression of I(to) channels. 相似文献
4.
西洛他唑对人心房肌细胞瞬间外向钾电流的影响 总被引:2,自引:0,他引:2
目的:观察西洛他唑对人心房肌细胞瞬间外向钾电流(Ito1)的影响,探讨该药抗心律失常作用的机制.方法:二步酶解法分离人单个右心房肌细胞,应用全细胞膜片钳技术记录人心房肌细胞Ito1.结果:在保持电位-50 mV和去极化脉冲为 50 mV条件下,30 μmol/L西洛他唑显著降低Ito1,使Ito1幅值由加药前(8.16±0.70)pA/pF降至(4.84±0.60)pA/pF(P<0.01).西洛他唑在1~50 μmol/L范围内呈浓度依赖性的抑制Ito1,1 μmol/L时即产生作用,50 μmol/L时达最大效应(降低51.09%±3.00%),IC50为(13.18±2.60)μmol/L.此外,该药对Ito1的电压依赖性激活和失活曲线以及恢复曲线均无显著影响.结论:本实验结果表明西洛他唑浓度依赖性地阻滞人心房肌细胞的Ito1. 相似文献
5.
Evyatar Av-Ron 《Journal of mathematical biology》1994,33(1):71-87
Presented here is a biophysical cell model which can exhibit low-frequency repetitive activity and bursting behavior. The
model is developed from previous models (Av-Ron et al. 1991, 1993) for excitability, oscillations and bursting. A stepwise
development of the present model shows the contribution of a transient potassium current (I
A
) to the overall dynamics. By changing a limited set of model parameters one can describe different firing patterns; oscillations
with frequencies ranging from 2–200 Hz and a wide range of bursting behaviors in terms of the durations of bursting and quiescence,
peak firing frequency and rate of change of the firing frequency. 相似文献
6.
Aminopyridines block an inactivating potassium current having slow recovery kinetics. 总被引:3,自引:0,他引:3
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The blocking action of aminopyridines on an inactivating K current (lKi) in GH3 pituitary cells was studied before and after altering the macroscopic decay of the current with N-bromoacetamide (NBA). The first depolarizing pulse delivered either seconds or minutes after beginning 4-aminopyridine (4AP) application, elicited a current with both a more rapid decay and a reduced peak amplitude. The rapid decay (or time-dependent block) was especially prominent in NBA-treated cells. With continued drug application, subsequent test pulses revealed a stable block of peak current, greater in NBA-treated than control cells. Recovery from block was enhanced by hyperpolarizing holding potentials and by the first depolarizing pulse delivered after prolonged recovery intervals. Unlike aminopyridine block of other K currents, there was no convincing evidence for voltage shifts in activation or inactivation, or for voltage and frequency-dependent unblock. Increasing the open probability of the channels did, however, facilitate the block. Although the behavior of currents in 4AP was suggestive of "open channel block," the block was not produced by 4-aminopyridine methiodide, a positively charged aminopyridine. Moreover, because partial block and recovery occurred without opening the channels we suggest that aminopyridines bind to, or near, this K channel, that this binding is enhanced by opening the channel, and that a conformational change is induced which mimics inactivation. Because recovery from block is enhanced by negative potentials, we suggest that aminopyridine molecules may become "trapped" by inactivation awaiting the slow process of reactivation to escape their binding sites. 相似文献
7.
Hulme JT Orchard CH 《American journal of physiology. Heart and circulatory physiology》2000,278(1):H50-H59
The effect of acidosis on the transient outward K(+) current (I(to)) of rat ventricular myocytes has been investigated using the perforated patch-clamp technique. When the holding potential was -80 mV, depolarizing pulses to potentials positive to -20 mV activated I(to) in subepicardial cells but activated little I(to) in subendocardial cells. Exposure to an acid solution (pH 6.5) had no significant effect on I(to) activated from this holding potential in either subepicardial or subendocardial cells. When the holding potential was -40 mV, acidosis significantly increased I(to) at potentials positive to -20 mV in subepicardial cells but had little effect on I(to) in subendocardial cells. The increase in I(to) in subepicardial cells was inhibited by 10 mM 4-aminopyridine. In subepicardial cells, acidosis caused a +8.57-mV shift in the steady-state inactivation curve. It is concluded that in subepicardial rat ventricular myocytes acidosis increases the amplitude of I(to) as a consequence of a depolarizing shift in the voltage dependence of inactivation. 相似文献
8.
Kv4.2通道电流与大鼠海马神经元瞬间外向钾电流特性的比较 总被引:3,自引:0,他引:3
本研究比较了转染的Kv4.2钾电流与原代培养大鼠海马神经元上瞬间外向钾电流(IA)动力学特征。实验采用瞬时转染,细胞培养和全细胞膜片钳记录等方法。结果表明:转染的Kv4.2通道电流和海马神经元上IA均具有明显的A型电流特征。海马神经元IA的半数最大激活电位和斜率因子分别为-10.0±3.3 mV和13.9±2.6 mV;半数最大失活电位和斜率因子分别为-93.0±11.4 mV和-9.0±1.5 mV;失活后再激活恢复时间常数(T)为27.9±14.1 ms。Kv4.2的半数最大激活电位和斜率因子分别为-9.7±4.1 mV和15.8±5.7 mV;半数最大失活电位和斜率因子分别为-59.4±12.2 mV和8.0±3.1 mV;Kv4.2的灭活后再激活的恢复时间常数τ为172.8±10.0 ms。结果提示:Kv4.2通道电流可能是海马神经元上的IA电流的主要成分,但不是唯一成分。 相似文献
9.
《The Journal of general physiology》1993,101(4):603-626
Block of the calcium-independent transient outward K+ current, I(to), by 4-aminopyridine (4-AP) was studied in ferret right ventricular myocytes using the whole cell patch clamp technique. 4-AP reduces I(to) through a closed state blocking mechanism displaying "reverse use- dependent" behavior that was inferred from: (a) development of tonic block at hyperpolarized potentials; (b) inhibition of development of tonic block at depolarized potentials; (c) appearance of "crossover phenomena" in which the peak current is delayed in the presence of 4-AP at depolarized potentials; (d) relief of block at depolarized potentials which is concentration dependent and parallels steady-state inactivation for low 4-AP concentrations (V1/2 approximately -10 mV in 0.1 mM 4-AP) and steady-state activation at higher concentrations (V1/2 = +7 mV in 1 mM 4-AP, +15 mV in 10 mM 4-AP); and (e) reassociation of 4- AP at hyperpolarized potentials. No evidence for interaction of 4-AP with either the open or inactivated state of the I(to) channel was obtained from measurements of kinetics of recovery and deactivation in the presence of 0.5-1.0 mM 4-AP. At hyperpolarized potentials (-30 to - 90 mV) 10 mM 4-AP associates slowly (time constants ranging from approximately 800 to 1,300 ms) with the closed states of the channel (apparent Kd approximately 0.2 mM). From -90 to -20 mV the affinity of the I(to) channel for 4-AP appears to be voltage insensitive; however, at depolarized potentials (+20 to +100 mV) 4-AP dissociates with time constants ranging from approximately 350 to 150 ms. Consequently, the properties of 4-AP binding to the I(to) channel undergo a transition in the range of potentials over which channel activation and inactivation occurs (-30 to +20 mV). We propose a closed state model of I(to) channel gating and 4-AP binding kinetics, in which 4-AP binds to three closed states. In this model 4-AP has a progressively lower affinity as the channel approaches the open state, but has no intrinsic voltage dependence of binding. 相似文献
10.
Effects of cyhalothrin on the transient outward potassium current in central neurons of Helicoverpa armigera 总被引:1,自引:0,他引:1
YONG WANG BING-JUN HE QIANG ZHAO ZHI LIANG AN-XI LIU 《Insect Science》2006,13(1):13-17
The effects of cyhalothrin on the transient outward potassium current in central neurons of Helicoverpa armigera were studied by using the patch clamp techniques. The results showed that before using cyhalothrin (10.5 mmol/L), activation potential was approximately -40 mV, after application of the drug, the activation potential shifted roughly 10 mV to the negative potential direction, so channels can be activated more easily. Before and after cyhalothrin application, the change of current amplitude was insignificant. The value of V1/2 and k of activation curves did not change significantly, however, the V1/2 of the inactivation curves changed significantly. Inactivation curves significantly shifted to a negative direction, so that inactivation of the channels was hastened. It is indicated that there may exit a primary way in which cyhalothrin provides neurotoxicity to the nervous system through the regulation of activation potentials and inactivation state of IA channels. 相似文献
11.
R Bardoni O Belluzzi 《Bollettino della Società italiana di biologia sperimentale》1991,67(12):1015-1021
Thin slices were prepared from cerebella of 10-24 day old rats and examined with whole-cell patch-clamp methods. Depolarizing steps from holding potentials negative to -60 mV elicited an early transient outward current, identified as IA, and a late outward K+ current. Depolarizations from -50 mV failed to evoke any A current and gave only a slowly rising component similar to the delayed K+ current, which inactivated thereafter with a time constant of 2.5 s at -30 mV. The IA peaked in 1-2 ms, decayed following a double exponential with time constants of 8.1 and 53.2 ms at +20 mV and was half-inactivated at -82.5 mV. 4-AP 4 mM depressed both K+ currents showing little specificity between them, while TEA 20 mM selectively abolished only the delayed K+ current. 相似文献
12.
Distinct transient outward potassium current (Ito) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes 总被引:9,自引:0,他引:9
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Brahmajothi MV Campbell DL Rasmusson RL Morales MJ Trimmer JS Nerbonne JM Strauss HC 《The Journal of general physiology》1999,113(4):581-600
The biophysical characteristics and alpha subunits underlying calcium-independent transient outward potassium current (Ito) phenotypes expressed in ferret left ventricular epicardial (LV epi) and endocardial (LV endo) myocytes were analyzed using patch clamp, fluorescent in situ hybridization (FISH), and immunofluorescent (IF) techniques. Two distinct Ito phenotypes were measured (21-22 degrees C) in the majority of LV epi and LV endo myocytes studied. The two Ito phenotypes displayed marked differences in peak current densities, activation thresholds, inactivation characteristics, and recovery kinetics. Ito,epi recovered rapidly [taurec, -70 mV = 51 +/- 3 ms] with minimal cumulative inactivation, while Ito,endo recovered slowly [taurec, -70 mV = 3,002 +/- 447 ms] with marked cumulative inactivation. Heteropoda toxin 2 (150 nM) blocked Ito,epi in a voltage-dependent manner, but had no effect on Ito,endo. Parallel FISH and IF measurements conducted on isolated LV epi and LV endo myocytes demonstrated that Kv1.4, Kv4.2, and Kv4.3 alpha subunit expression in LV myocyte types was quite heterogenous: (a) Kv4.2 and Kv4.3 were more predominantly expressed in LV epi than LV endo myocytes, and (b) Kv1.4 was expressed in the majority of LV endo myocytes but was essentially absent in LV epi myocytes. In combination with previous measurements on recovery kinetics (Kv1.4, slow; Kv4.2/4.3, relatively rapid) and Heteropoda toxin block (Kv1.4, insensitive; Kv4.2, sensitive), our results strongly support the hypothesis that, in ferret heart, Kv4.2/Kv4.3 and Kv1.4 alpha subunits, respectively, are the molecular substrates underlying the Ito,epi and Ito,endo phenotypes. FISH and IF measurements were also conducted on ferret ventricular tissue sections. The three Ito alpha subunits again showed distinct patterns of distribution: (a) Kv1.4 was localized primarily to the apical portion of the LV septum, LV endocardium, and approximate inner 75% of the LV free wall; (b) Kv4. 2 was localized primarily to the right ventricular free wall, epicardial layers of the LV, and base of the heart; and (c) Kv4.3 was localized primarily to epicardial layers of the LV apex and diffusely distributed in the LV free wall and septum. Therefore, in intact ventricular tissue, a heterogeneous distribution of candidate Ito alpha subunits not only exists from LV epicardium to endocardium but also from apex to base. 相似文献
13.
Preferential expression of transient potassium current (IA) by 'short' hair cells of the chick's cochlea 总被引:2,自引:0,他引:2
We have made a comparative study of the membrane properties of tall and short hair cells isolated from a selected region of the chick's cochlea. Tall hair cells are analogous to inner cochlear hair cells of mammals, and like those, are presynaptic to the majority of afferent neurons in the cochlea. Short hair cells, like mammalian outer hair cells, are the postsynaptic targets of efferent neurons that inhibit the cochlea. Voltage-clamp recordings have revealed that short hair cells have an inactivating potassium (K) current, IA, whereas tall hair cells have little or none. Short hair cells are also sensitive to the cholinergic agonist carbachol, whereas tall hair cells are not. This pattern is in accord with the selective distribution of efferent cholinergic synapses in the cochlea. Although IA is completely inactivated at the resting potential of the short hair cells, cholinergic agonists can hyperpolarize these cells by as much as 30 mV. This hyperpolarization removes inactivation and allows IA to modulate subsequent voltage-dependent processes in short hair cells. It is concluded that IA could increase the high frequency response of the hair cell by decreasing membrane resistance and thus the membrane time constant after inhibition. This will be of particular importance to cochlear function if short hair cells produce voltage-dependent movements, as do mammalian outer hair cells. 相似文献
14.
J R Howe M Baker J M Ritchie 《Proceedings. Biological sciences / The Royal Society》1992,249(1326):309-316
Currents through delayed rectifier-type K+ channels in Schwann cells cultured from rabbit sciatic nerve were studied with patch-clamp techniques. When the internal and external solutions contained physiological concentrations of sodium, the amplitude of these outward currents declined as the cell was depolarized to potentials above about +40 mV, despite the increased driving force. This reduction in the amplitude of outward K+ currents was observed in many cells before the subtraction of leakage currents; it was also observed for ensemble currents recorded in outside-out patches. It was therefore not the result of a leak-subtraction artefact nor of inadequate voltage-clamp control. Several lines of evidence also suggested that it was not the result of the extracellular accumulation of K+. By contrast, when the Na+ ion concentration of the internal solution was nominally zero, the reduction in the amplitude of outward K+ currents at positive membrane potentials was not observed. The apparent amplitude of single-channel currents through two types of K+ channel was reduced by 30 mM internal Na+, apparently as the result of a rapid 'flickery' block. The results suggest that channel block by internal Na+ is largely responsible for the negative slope conductance seen in current-voltage plots of whole-cell K+ currents at positive membrane potentials. In addition, our analysis of single-channel currents suggests that the current-voltage curve for a delayed rectifier channel in rabbit Schwann cells (in the absence of internal Na+) is roughly linear with internal and external K+ concentrations of 140 mM and 5.6 mM, respectively. 相似文献
15.
Modulation of the voltage-dependent transient outward potassium current (IA) by Pb2+ was studied in acutely dissociated rat hippocampal pyramidal cells from the CA1 region at postnatal ages 7-14 days using the conventional whole-cell patch-clamp technique. In the presence of different concentrations of external Pb2+, the initial delay and activation time of IA were concentration-dependently lengthened. In particular, the initial delay was even longer in 1 mM Pb2+, showing no signs of saturation. Pb2+ also slowed the inactivation of IA, for decay time constants in the presence of Pb2+ were increased under the same experimental protocols. The activation curves, which were reasonably fitted by a single Boltzmann function, illustrated that Pb2+ increased the voltage threshold of IA and shifted the normalized activation current-voltage curves to more depolarizing voltage commands. Moreover, Pb2+ significantly affected the steady-state inactivation of IA. The application of Pb 2+ made the curves of the steady-state inactivation of IA shift to more depolarizing voltages with little change in the slopes factors. In brief, the results demonstrated that Pb2+ is a dose- and voltage-dependent, reversible blocker of IA currents of hippocampal CA1 neurons. The observations were fitted by the revised "Kuo and Chen type model", which postulates a Pb2+-selective site near the pore of the IA channel and that modulation of the IA channel by Pb2+ is the result of the competitive influences of Pb2+ on opening and inactivating different pathways. 相似文献
16.
谷氨酸对大鼠海马CA1区神经元的短暂性外向K+电流的影响 总被引:7,自引:0,他引:7
为了在离子通道水平探讨谷氨酸对急性分离海马CA1区神经元的短暂外向K+电流的影响。用7~10d大鼠,以链霉蛋白酶E酶解加吸管吹打法制备海马CA1区神经元;利用全细胞膜片箝技术,观察了谷氨酸对海马CA1区锥体细胞的短暂性K+电流的影响。结果观察到谷氨酸对短暂性K+电流有明显抑制作用,且呈明显浓度依赖性、时间依赖性和部分电压依赖性。上述结果表明,谷氨酸对K+通道的影响在中枢神经系统中具有重要作用。 相似文献
17.
Fernández-Velasco M Ruiz-Hurtado G Hurtado O Moro MA Delgado C 《American journal of physiology. Heart and circulatory physiology》2007,293(1):H238-H245
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in the pathogenesis of heart failure. Prolongation of the action potential duration and downregulation of several K(+) currents might participate in the genesis of arrhythmias associated with chronic heart failure. Little information is available related to the mechanism by which TNF-alpha modulates cardiac K(+) channels. The present study analyzes the effect of TNF-alpha on the transient outward K(+) current (I(to)) in rat ventricular myocytes, using the whole cell patch-clamp technique. We found that TNF-alpha is able to induce a significant reduction of I(to) density, modifies its inactivation, and downregulates the Kv4.2 protein expression, while calcium current density is not affected. We have also demonstrated that the reduction of I(to) density induced by TNF-alpha was prevented by the selective inducible nitric oxide synthase (iNOS) inhibitor 1400-W, the protein synthesis inhibitor cycloheximide, the antioxidant tocopherol, and the superoxide dismutase mimetic manganese(III) tetrakis (4-benzoic acid) porphyrin. In addition, a reduced I(to) density was recorded in ventricular myocytes exposed to peroxynitrite, supporting a possible participation of this oxidant in the effects of TNF-alpha on I(to). We conclude that TNF-alpha exposure, through iNOS induction and generation of oxidant species, promotes electrophysiological changes (decreased I(to) and action potential duration prolongation) in rat ventricular myocytes, providing new insights into how cytokines modulate K(+) channels in the heart. 相似文献
18.
Chemical sympathetic denervation, suppression of myocardial transient outward potassium current, and ventricular fibrillation in the rat 总被引:1,自引:0,他引:1
Bai J Ren C Hao W Wang R Cao JM 《Canadian journal of physiology and pharmacology》2008,86(10):700-709
Sympathetic denervation is frequently observed in heart disease. To investigate the linkage of sympathetic denervation and cardiac arrhythmia, we developed a rat model of chemical sympathectomy by subcutaneous injections of 6-hydroxydopamine (6-OHDA). Cardiac sympathetic innervation was visualized by means of a glyoxylic catecholaminergic histofluorescence method. Transient outward current (Ito) of ventricular myocytes was recorded with the whole-cell configuration of the patch clamp technique. We observed that sympathectomy (i) decreased cardiac sympathetic nerve density and norepinephrine level, (ii) reduced the protein expression of Kv4.2, Kv1.4, and Kv channel-interacting protein 2 (KChIP2), (iii) decreased current densities and delayed activation of Ito channels, (iv) reduced the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element-binding protein (CREB), and (v) increased the severity of ventricular fibrillation induced by rapid pacing. Three weeks after 6-OHDA injections, which allowed time for sympathetic regeneration, we found cardiac sympathetic nerve density, norepinephrine levels, expression levels of Kv4.2 and KChIP2 proteins, and I(to) densities were partially normalized and ventricular fibrillation severity was decreased. We conclude that chemical sympathectomy downregulates the expression of selective Kv channel subunits and decreases myocardial I(to) channel activities, contributing to the elevated susceptibility to ventricular fibrillation. 相似文献
19.
S R Bolsover 《The Journal of general physiology》1981,78(6):617-636
When barnacle lateral eye photoreceptors are depolarized to membrane potentials of 0 to +50 mV in the dark, the plot of outward current through the cell membrane against time has two distinct maxima. The first maximum occurs 5-10 ms after the depolarization began. The current then decays to a minimum at approximately 500 ms after the onset of depolarization, and then increases to a second maximum 4-6 s after the depolarization began. If depolarization is maintained, the current again decays to reach a steady value approximately 1 min after depolarization began. The increase in current to the maximum at 4-6s from the minimum at approximately 500 ms is termed the "late current." It is maximum for depolarizations to around +25 mV and is reduced in amplitude at more positive potentials. It is not observed when the membrane is depolarized to potentials more positive than +60 mV. The late current is inhibited by external cobaltous ion and external tetraethylammonium ion, and shows a requirement for external calcium ion. When the calcium-sequestering agent EGTA is injected, the late current is abolished. Illumination of a cell under voltage clamp reduces the amplitude of the late current recorded subsequently in the dark. On the basis of the voltage dependence and pharmacology of the late current, it is proposed that the current is a calcium-dependent potassium current. 相似文献
20.
Many effects of short-chain phospholipids and n-alkanes on the squid axon sodium current (I
Na) are consistent with mechanisms involving changes in membrane thickness. Here, we suggest that the actions of short-chain phospholipids on an A-type potassium current (I
A
) in two-microelectrode voltage clamped Helix D1 and F77 neurons are incompatible with such simple mechanisms. Diheptanoyl phosphatidylcholine (diC7PC, 0.2 and 0.3 mm) caused substantial (58 and 79%), and in some cases partially reversible, increases in I
A
amplitude. These were correlated with hyperpolarizing shifts of up to –7 mV in the voltage dependence of current activation. The voltage dependence of steady-state inactivation was also moved in the hyperpolarizing direction. These effects are the opposite of those described for squid I
Na. 0.5 Saturated n-pentane and saturated n-hexane caused significant (–3 and –6 mV) hyperpolarizing shifts in the voltage dependence of I
A
inactivation, qualitatively consistent with their effects on squid I
Na, while the voltage dependence of activation was moved slightly to the left or unchanged. Hydrocarbons had variable effects on peak current amplitude, although saturated n-pentane produced a clear suppression. DiC7PC caused a 25% increase in the time constant of macroscopic I
A
inactivation (
b
) but 0.5 saturated n-pentane and saturated n-hexane reduced
b
by 40%. The effects of these agents on current-clamped cells were broadly consistent with their opposing actions on
b
—phospholipids tended to reduce excitability and n-alkanes tended to increase it. Possible mechanisms of I
A
perturbation are discussed.We gratefully acknowledge financial support from the Science and Engineering Research Council and the Wellcome Trust. We would also like to thank Prof. H. Meves, Dr. N. Franks and Dr. W. Lieb for helpful discussions. 相似文献