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Functional Characterization of a Cloned Human Intermediate‐Conductance Ca2+‐Activated K+ Channel

a-activated K channels are almost ubiquitously distributed in mammalian cells and constitute a major link between second-messenger systems and the electrical activity of the cell. Based on their electrophysiological characteristics, three major classes of Caactivated K channels have been described: large-conductance channels (BK), smallconductance channels (SK), and intermediate-conductance channels (IK). Each type of channel shows a distinct pharmacology and expression pattern. Unlike SK and BK channels, IK is absent in excitable tissues, but its presence has been demonstrated in red blood cells, Band T-lymphocytes, endothelial cells, as well as cells derived from epithelia. hIK is known to participate in the pathological dehydration of sickle cells, making it a possible target in treatment of sickle cell anemia. In salt-transporting tissues IK channels are believed to play a universal role in epithelial function, and therefore pharmacological modulators of hIK might be used in the therapy of secretory disorders like diarrhea. In addition, blockade of Ca-activated K channels in T-lymphocytes has been shown to prevent secondary immune responses, which demonstrate the possible relevance of IK modulators in treatment of immune disorders. In order to identify novel hIK channel modulators a high throughput fluorescence-based assay was developed.