The Sodium-Activated Potassium Channel Is Encoded by a Member of the Slo Gene Family

Abstract

Na +-activated potassium channels (K Na) have been identified in cardiomyocytes and neurons where they may provide protection against ischemia. We now report that K Na is encoded by the rSlo2 gene (also called Slack), the mammalian ortholog of slo-2 in C. elegans. rSlo2, heterologously expressed, shares many properties of native K Na including activation by intracellular Na +, high conductance, and prominent subconductance states. In addition to activation by Na +, we report that rSLO-2 channels are cooperatively activated by intracellular Cl −, similar to C. elegans SLO-2 channels. Since intracellular Na + and Cl − both rise in oxygen-deprived cells, coactivation may more effectively trigger the activity of rSLO-2 channels in ischemia. In C. elegans, mutational and physiological analysis revealed that the SLO-2 current is a major component of the delayed rectifier. We demonstrate in C. elegans that slo-2 mutants are hypersensitive to hypoxia, suggesting a conserved role for the slo-2 gene subfamily.