Activation kinetics of the slow afterhyperpolarization in hippocampal CA1 neurons

Activation kinetics of the slow afterhyperpolarization in hippocampal CA1 neurons
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DOI:
10.1007/s00424-003-1237-2
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发表时间:
2004-05-01
影响因子:
4.5
通讯作者:
Adelman, JP
Adelman, JP
中科院分区:
医学3区
文献类型:
--
作者:
Gerlach, AC;Maylie, J;Adelman, JP

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采用全细胞记录法研究了快、中时程超极化抑制剂对CA 1区神经元慢后超极化(sAHP)的激活作用。缓慢后超极化电流(IsAHP)的幅度增加的功能的持续时间和幅度的去极化电压脉冲反映梯度增加的Ca 2+内流通过电压依赖性Ca 2+通道。因此,根据IsAHP家族确定的激活时间常数tau(max)是脉冲持续时间的函数,在-20至20 mV范围内呈电压依赖性降低数倍,并依赖于细胞外[Ca 2 +]。IsAHP显示出明显的上升阶段,其通过具有时间常数tau(上升)的单个指数很好地拟合,该时间常数不随脉冲持续时间、电压、IsAHP振幅或外部[Ca 2 +]变化,并且显著慢于tau(最大值)。在电流钳中,sAHP的幅度随着诱发动作电位的数目而增加,但sAHP的tau(rise)与动作电位数目无关,并且与电压钳中记录的IsAHP的tau(rise)相似。结果表明,有两个组件的发展IsAHP,一个快速的,电压和Ca 2+依赖的步骤,其幅度和速率反映了电压依赖的Ca 2+通道,触发第二限速,电压无关的过程,决定了缓慢的IsAHP上升动力学。
The activation of the slow afterhyperpolarization (sAHP) in CA1 neurons was studied using whole-cell recordings in the presence of inhibitors of the fast and medium-duration AHPs. The amplitude of the slow afterhyperpolarization current (IsAHP) increased as a function of duration and magnitude of the depolarizing voltage pulse reflecting graded increases in Ca2+ influx through voltage-dependent Ca2+ channels. Therefore, the time constant for activation, tau(max), determined from a family of IsAHPs as a function of pulse duration, was voltage dependent decreasing several-fold within the range of -20 to 20 mV and was dependent on extracellular [Ca2+]. The IsAHP displayed a pronounced rising phase that was well fit by a single exponential with a time constant, tau(rise), that was invariant of pulse duration, voltage, IsAHP amplitude, or external [Ca2+] and was significantly slower than the tau(max). In current clamp, the magnitude of the sAHP increased with the number of evoked action potentials, yet tau(rise) of the sAHP was invariant of action potential number and was similar to the tau(rise) of the IsAHP recorded in voltage-clamp. The results suggest that there are two components to the development of the IsAHP, a rapid, voltage- and Ca2+-dependent step, the magnitude and rate of which reflects the voltage dependence of the Ca2+ channels, that triggers a second rate-limiting, voltage-independent process that dictates the slow IsAHP rise kinetics.