DIRECT MEASUREMENT OF L-TYPE CA2+ WINDOW CURRENT IN HEART-CELLS
DIRECT MEASUREMENT OF L-TYPE CA2+ WINDOW CURRENT IN HEART-CELLS
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DOI：
10.1161/01.res.70.3.445
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发表时间：
1992-03-01
影响因子：
20.1
通讯作者：
JANUARY, CT
中科院分区：
文献类型：
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作者：
HIRANO, Y;MOSCUCCI, A;JANUARY, CT
几个离子通道电流的激活和失活关系重叠，表明存在稳态或“窗口”电流。我们研究了L-型钙离子通道窗口电流在单个心脏浦肯野细胞使用电压钳协议，该通道首先失活几乎完全在一个长时间的去极化步骤，然后恢复钙离子电流在复极步骤中观察到的L-型钙离子窗口电压范围。在这些条件下，一个小幅度的内向钙电流逐渐复极后的窗口内的电压，但不是在步骤后的电压正或负。窗口电流被抑制镉（50 μ M），硝苯地平（1 μ M），尼卡地平（1 μ M），并增加了异丙肾上腺素（5 μ M）和湾K 8644（1 μ M）。在窗口电流发展的电压下，L型Ca 2+通道也恢复到关闭状态，它们可以通过额外的去极化步骤重新打开。在窗口范围为正的电压下，通道恢复到闭合状态是不存在的，而在窗口范围为负的电压下，通道恢复到闭合状态增加，正如“稳态”失活关系所预期的那样。我们的研究结果提供了直接测量L-型钙窗口电流，并将其与其他过程，如缓慢失活区分开来。我们的研究结果支持的假设，在一个窗口内发生通道转换从失活到关闭状态，这些通道（重新）开放，这个过程可能会重复发生。讨论了L型Ca 2+窗口电流的一些生理和病理生理作用。
The activation and inactivation relations of several ion channel currents overlap, suggesting the existence of a steady-state or "window" current. We studied L-type Ca2+ channel window current in single cardiac Purkinje cells using a voltage-clamp protocol by which channels were first inactivated nearly completely during a long-duration depolarizing step, and then the recovery of Ca2+ current was observed during repolarizing steps into the L-type Ca2+ window voltage range. With these conditions, a small-amplitude inward Ca2+ current gradually developed after repolarization to voltages within the window but not after steps to voltages positive or negative to it. Window current was suppressed by Cd2+ (50-mu-M), nifedipine (1-mu-M), and nicardipine (1-mu-M), and it was augmented by isoproterenol (5-mu-M) and Bay K 8644 (1-mu-M). At voltages at which window current developed, L-type Ca2+ channels also recovered to a closed state from which they could be reopened by an additional depolarizing step. At voltages positive to the window range, channel recovery to a closed state(s) was absent, whereas at voltages negative to the window range, channel recovery to a closed state(s) increased, as expected from the "steady-state" inactivation relation. Our results provide direct measurement of L-type Ca2+ window current and distinguish it from other processes, such as slow inactivation. Our findings support the postulate that within a window there occur channel transitions from inactivated to closed states, and these channels (re)open, and this process may occur repetitively. Some physiological and pathophysiological roles for L-type Ca2+ window current are discussed.