Small-conductance calcium-activated potassium channels
Small-conductance calcium-activated potassium channels
复制标题
DOI：
10.1111/j.1749-6632.1999.tb11298.x
复制
发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Adelman, JP
中科院分区：
文献类型：
--
作者：
Bond, CT;Maylie, J;Adelman, JP
SK通道在所有可兴奋细胞中起着重要作用。SK通道是钾选择性的，并且通过细胞内钙水平的增加来激活，例如在动作电位期间发生。它们的激活引起膜超极化，从而抑制细胞收缩并限制重复动作电位的放电频率。由动作电位放电引起的细胞内钙增加缓慢衰减，允许SK通道激活产生称为缓慢后超极化（sAHP）的持久超极化。这种尖峰频率适应保护细胞免受持续强直活动的有害影响，并且对于正常神经传递是必需的。根据对蜂毒毒素apamin的敏感性，慢AHPs可以分为两组。一般来说，apamin敏感的sAHP在单个动作电位后迅速激活，并以约150 ms的时间常数衰减。相比之下，apamin不敏感的sAHP缓慢上升，并以约1.5 s的时间常数衰减。apamin敏感和apamin不敏感的Sg通道最近已被克隆。本章将比较不同类别的sAHPs，讨论克隆的SK通道，以及它们是如何被钙离子门控的，描述它们不同药理学的分子基础，并回顾SK通道在几种病理条件下可能发挥的作用。
SK channels play a fundamental role in all excitable cells. SK channels are potassium selective and are activated by an increase in the level of intracellular calcium, such as occurs during an action potential. Their activation causes membrane hyperpolarization, which inhibits cell hiring and limits the firing frequency of repetetive action potentials. The intracellular calcium increase evoked by action potential firing decays slowly, allowing SK channel activation to generate a long-lasting hyperpolarization termed the slow afterhyperpolarization (sAHP), This spike-frequency adaptation protects the cell from the deleterious effects of continuous tetanic activity and is essential for normal neurotransmission. Slow AHPs can be classified into two groups, based on sensitivity to the bee venom toxin apamin. In general, apamin-sensitive sAHPs activate rapidly following a single action potential and decay with a time constant of approximately 150 ms. In contrast, apamin-insensitive sAHPs rise slowly and decay with a time constant of approximately 1.5 s, The basis for this kinetic difference is not yet understood. Apamin-sensitive and apamin insensitive Sg channels have recently been cloned. This chapter will compare with different classes of sAHPs, discuss the cloned SK channels and how they are gated by calcium ions, describe the molecular basis for their different pharmacologies, and review the possible role of SK channels in several pathological conditions.