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Significant advances have recently been made in our understanding of the biology of small conductance calcium-activated potassium channels (SK channels). Although a long time ‘Cinderella’ to the better characterized large conductance BK channel, renewed interest in SK channels has been sparked by the recent cloning of several subtypes of this important potassium channel. The information gained from our improved understanding of the molecular nature of SK channels is already helping to elucidate the molecular basis of drug interactions, as well as to further define the physiological function and tissue distribution of these channels. Characterization of SK channels is also being aided by the availability of a wider variety of pharmacological tools including peptide toxins and potent synthetic small molecules. The contribution of SK channels to physiology and pathophysiology of CNS, skeletal and smooth muscle function clearly points to the future importance of these channels as targets for drug development.