BK Channel Regulation of Afterpotentials and Burst Firing in Cerebellar Purkinje Neurons
BK Channel Regulation of Afterpotentials and Burst Firing in Cerebellar Purkinje Neurons
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DOI：
10.1523/jneurosci.0192-20.2021
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发表时间：
2021-03-31
影响因子：
5.3
通讯作者：
Bean, Bruce P.
中科院分区：
文献类型：
--
作者：
Niday, Zachary;Bean, Bruce P.
BK钙激活钾通道具有复杂的动力学，因为它们被电压和细胞质钙激活。动作电位过程中BK激活和失活的时间决定了它们在调节放电模式中的功能作用，但难以先验预测。我们使用动作电位钳来表征来自两种性别小鼠的浦肯野神经元的动作电位期间电压依赖性钙电流和BK电流的动力学，使用在37 ℃下启用快速电压钳的急性分离的神经元。在去极化电压阶跃和动作电位波形下，BK电流完全依赖于通过电压依赖性钙通道的钙进入。电压阶跃，BK电流大大超过触发钙电流，只有一个简短的，小的净内向钙电流之前，钙激活BK电流占主导地位的总钙依赖性电流。在动作电位波形，虽然BK电流激活后，只有一个很短的（类似于100 μ s）延迟钙电流，这两个电流在很大程度上是分开的，与钙电流流动的下降阶段的动作电位和大多数BK电流流动后复极几毫秒。阶跃去极化激活了具有快速激活和失活动力学的伊比利亚毒素敏感的BK组分和较慢门控的伊比利亚毒素抗性组分。然而，在动作电位放电过程中，几乎所有的BK电流都来自门控更快的伊比利亚毒素敏感通道，即使在动作电位爆发期间也是如此。抑制BK电流对动作电位宽度或快速后超极化影响不大，但可将中等后超极化转换为后去极化，并可将单一动作电位的紧张性放电转换为爆发性放电。
BK calcium-activated potassium channels have complex kinetics because they are activated by both voltage and cytoplasmic calcium. The timing of BK activation and deactivation during action potentials determines their functional role in regulating firing patterns but is difficult to predict a priori. We used action potential clamp to characterize the kinetics of voltage-dependent calcium current and BK current during action potentials in Purkinje neurons from mice of both sexes, using acutely dissociated neurons that enabled rapid voltage clamp at 37 degrees C. With both depolarizing voltage steps and action potential waveforms, BK current was entirely dependent on calcium entry through voltage-dependent calcium channels. With voltage steps, BK current greatly outweighed the triggering calcium current, with only a brief, small net inward calcium current before Ca-activated BK current dominated the total Ca-dependent current. During action potential waveforms, although BK current activated with only a short (similar to 100 mu s) delay after calcium current, the two currents were largely separated, with calcium current flowing during the falling phase of the action potential and most BK current flowing over several milliseconds after repolarization. Step depolarizations activated both an iberiotoxin-sensitive BK component with rapid activation and deactivation kinetics and a slower-gating iberiotoxin-resistant component. During action potential firing, however, almost all BK current came from the faster-gating iberiotoxin-sensitive channels, even during bursts of action potentials. Inhibiting BK current had little effect on action potential width or a fast afterhyperpolarization but converted a medium afterhyperpolarization to an afterdepolarization and could convert tonic firing of single action potentials to burst firing.