Vergara C, Latorre R, Marrion N V, Adelman J P
Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
Curr Opin Neurobiol. 1998 Jun;8(3):321-9. doi: 10.1016/s0959-4388(98)80056-1.
Calcium-activated potassium channels are fundamental regulators of neuronal excitability, participating in interspike interval and spike-frequency adaptation. For large-conductance calcium-activated potassium (BK) channels, recent experiments have illuminated the fundamental biophysical mechanisms of gating, demonstrating that BK channels are voltage gated and calcium modulated. Structurally, BK channels have been shown to possess an extracellular amino-terminal domain, different from other potassium channels. Domains and residues involved in calcium-gating, and perhaps calcium binding itself, have been identified. For small- and intermediate-conductance calcium-activated potassium channels, SK and IK channels, clones have only recently become available, and they show that SK channels are a distinct subfamily of potassium channels. The biophysical properties of SK channels demonstrate that kinetic differences between apamin-sensitive and apamin-insensitive slow afterhyperpolarizations are not attributable to intrinsic gating differences between the two subtypes. Interestingly, SK and IK channels may prove effective drug targets for diseases such as myotonic muscular dystrophy and sickle cell anemia.
钙激活钾通道是神经元兴奋性的基本调节因子，参与峰间间隔和峰频率适应。对于大电导钙激活钾（BK）通道，最近的实验阐明了门控的基本生物物理机制，表明BK通道是电压门控和钙调制的。在结构上，BK通道已被证明具有细胞外氨基末端结构域，这与其他钾通道不同。已经确定了参与钙门控以及可能参与钙结合本身的结构域和残基。对于小电导和中电导钙激活钾通道，即SK和IK通道，克隆直到最近才可用，并且它们表明SK通道是钾通道的一个独特亚家族。SK通道的生物物理特性表明，蜂毒明肽敏感和蜂毒明肽不敏感的慢后超极化之间的动力学差异并非归因于两种亚型之间的内在门控差异。有趣的是，SK和IK通道可能被证明是治疗强直性肌营养不良和镰状细胞贫血等疾病的有效药物靶点。
