CALCIUM-ACTIVATED POTASSIUM CHANNELS

Calcium-activated potassium channels are fundamental regulators of neu ronal excitability, participating in interspike interval and spike-fre quency adaptation. For targe-conductance calcium-activated potassium ( BK) channels, recent experiments have illuminated the fundamental biop hysical mechanisms of gating, demonstrating that BK channels are volta ge gated and calcium modulated. Structurally, BK channels have been sh own to possess an extracellular amino-terminal domain, different from other potassium channels. Domains and residues involved in calcium-gat ing, and perhaps calcium binding itself, have been identified. For sma ll- and intermediate-conductance calcium-activated potassium channels, SK and IK channels, clones have only recently become available, and t hey show that SK channels are a distinct subfamily of potassium channe ls. The biophysical properties of SK channels demonstrate that kinetic differences between apamin-sensitive and apamin-insensitive slow afte rhyperpolarizations are not attributable to intrinsic gating differenc es between the two subtypes, Interestingly, SK and IK channels may pro ve effective drug targets for diseases such as myotonic muscular dystr ophy and sickle cell anemia.