Repolarizing responses of BKCa-Cav complexes are distinctly shaped by their Cav subunits
Repolarizing responses of BKCa-Cav complexes are distinctly shaped by their Cav subunits
复制标题
DOI：
10.1523/jneurosci.2274-08.2008
复制
发表时间：
2008-08-13
影响因子：
5.3
通讯作者：
Fakler, Bernd
中科院分区：
文献类型：
--
作者：
Berkefeld, Henrike;Fakler, Bernd
大电导钙离子和电压激活钾离子通道（BKCa）通过其复极化钾离子电导在许多类型的可兴奋细胞中形成放电模式。BK（Ca-）介导的电流的起始和持续时间通常由动作电位（AP）引发，似乎是细胞类型特异性的，并且显示在1 ms和高达几十毫秒之间变化。在最近的工作中，我们表明，在细胞条件下，BKCa通道的可靠激活是通过将其整合到与电压激活的Ca 2+（Cav）通道的复合物中来实现的，所述复合物提供浓度足够高（>= 10 μ M）的Ca 2+离子，用于在生理电压范围内激活BKCa。BKCa-Cav复合物的形成仅限于Cav通道的一个子集，Cav1.2（L型）和Cav2.1/2.2（P/Q型和N型），它们的表达模式和门控特性差异很大。在这里，我们重建不同的BKCa-Cav复合物在非洲爪蟾卵母细胞和培养细胞，并使用膜片钳记录比较BKCa-Cav 1.2和BKCa Cav 2. 1复合物的功能特性。在稳态条件下，由BKCa-Cav 2.1复合物介导的K+电流表现出相当快的上升时间，并在比由BKCa和Cav 1. 2形成的复合物明显更负的电位下达到最大值，这与两种Cav亚型的不同稳态激活和门控动力学一致。当AP波形用作电压命令时，BKCa-Cav 2. 1介导的K+电流发生在较短的AP处，并且持续时间长于BKCa-Cav 1.2。这些结果表明，通过BKCa-Cav复合物的复极化K+电流是由各自的Cav亚基形成的，并且不同的Cav通道可以使BKCa电流适应不同类型细胞的特定要求。
Large-conductance Ca2+- and voltage-activated potassium (BKCa) channels shape the firing pattern in many types of excitable cell through their repolarizing K+ conductance. The onset and duration of the BK(Ca-)mediated currents typically initiated by action potentials (APs) appear to be cell-type specific and were shown to vary between 1ms and up to a few tens of milliseconds. In recent work, we showed that reliable activation of BKCa channels under cellular conditions is enabled by their integration into complexes with voltage-activated Ca2+ (Cav) channels that provide Ca2+ ions at concentrations sufficiently high (>= 10 mu M) for activation of BKCa in the physiological voltage range. Formation of BKCa-Cav complexes is restricted to a subset of Cav channels, Cav1.2 (L-type) and Cav2.1/2.2 (P/Q- and N-type), which differ greatly in their expression pattern and gating properties. Here, we reconstituted distinct BKCa-Cav complexes in Xenopus oocytes and culture cells and used patch-clamp recordings to compare the functional properties of BKCa-Cav1.2 and BKCa Cav2.1 complexes. Under steady-state conditions, K+ currents mediated by BKCa-Cav2.1 complexes exhibit a considerably faster rise time and reach maximum at potentials markedly more negative than complexes formed by BKCa and Cav1.2, in line with the distinct steady-state activation and gating kinetics of the two Cav subtypes. When AP waveforms were used as a voltage command, K+ currents mediated by BKCa -Cav2.1 occurred at shorter APs and lasted longer than that of BKCa-Cav1.2. These results demonstrate that the repolarizing K+ currents through BKCa-Cav complexes are shaped by the respective Cav subunit and that the distinct Cav channels may adapt BKCa currents to the particular requirements of distinct types of cell.