Calcium current inactivation in insulin-secreting cells is mediated by calcium influx and membrane depolarization.
Calcium current inactivation in insulin-secreting cells is mediated by calcium influx and membrane depolarization.
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胰岛素分泌细胞中的钙电流失活是由钙流入和膜去极化介导的。
DOI：
10.1007/bf00585619
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Cook,DL
中科院分区：
文献类型：
--
作者：
Satin,LS;Cook,DL
在室温下，用全细胞膜片钳方法研究了单个、分离的胰岛素分泌HIT细胞电压钳制后电压依赖性钙电流的失活。河豚毒素、四乙基铵、ATP、4-氨基吡啶和Cs均能抑制Na和K电流。钙电流在小于10 ms内通过从−100 mV的保持电位超过−50 mV的去极化激活，并且与先前的研究一样，通过其对二价阳离子阻断的敏感性和对作为电荷载体的Ba的渗透性来识别。持续去极化揭示了两个动力学上不同的失活阶段：快速阶段在不到100 ms的时间内失活约50%的电流，而剩余的电流在接下来的10-20 s内失活。快速失活似乎是由于Ca ~（2+）内流，因为当Ba ~（2+）用作电流载体时，失活明显减慢，而失活程度随着去极化的增加而增加和减少，与内向Ca ~（2+）电流的U形电流-电压关系直接平行。慢失活似乎是电压依赖性的，因为电流可以被10 s长的去极化至低于激活Ca电流的阈值的电位而失活（约20%），慢失活的时间常数是电压依赖性的，并且当Ca被Ba取代时，慢失活持续存在。具有低激活阈值（在-50至-30 mV范围内）的Ca电流似乎优先被快速Ca依赖性机制灭活。恢复缓慢失活的钙电流是非常缓慢的和电流失活较大的去极化需要较长的恢复时间比那些引起的较小的去极化。快速和缓慢的失活机制可能是重要的，在了解快速尖峰和缓慢的平台去极化胰腺B细胞暴露于刺激水平的葡萄糖。
Inactivation of voltage-dependent calcium currents was studied in single, dissociated insulin-secreting HIT cells voltage-clamped by the whole-cell patch-clamp method at room temperature. Na and K currents were suppressed by tetrodotoxin, tetraethylammonium, ATP, 4-aminopyridine and Cs. Ca currents activated in less than 10 ms by depolarizations beyond −50 mV from a holding potential of −100 mV and were identified, as in previous studies, by their sensitivity to divalent cation blockade and permeability to Ba as a charge carrier. Sustained depolarization revealed two kinetically distinct phases of inactivation: a rapid phase inactivated approximately 50% of the current in less than 100 ms while the remaining current was inactivated over the next 10–20 s. Rapid inactivation appeared to be due to Ca2+influx since it was slowed markedly when Ba2+was used as the current carrier, while the degree of inactivation mercased and decreased with increasing depolarization in direct parallel with the U-shaped current-voltage relationship for inward Ca current. Slow inactivation appeared to be voltage-dependent since current could be inactivated (by ≈20%) by 10 s long depolarizations to potentials below the threshold for activating Ca current, slow time constants of inactivation were voltage-dependent and slow inactivation persisted when Ca was replaced with Ba. Ca currents with low activation thresholds (in the −50 to −30 mV range) appeared to be preferentially inactivated by the rapid Ca-dependent mechanism. Recovery of slowly inactivated Ca current was very slow and currents inactivated by larger depolarizations required longer recovery time than those elicited by smaller depolarizations. Rapid and slow inactivation mechanisms may be important in understanding the fast spiking and slow plateau depolarizations seen in pancreatic B-cells exposed to stimulatory levels of glucose.