Role of BK channels in hypertension and potassium secretion

Purpose of review This review summarizes recent studies of hypertension associated with a defect in renal K excretion due to genetic deletions of various components of the large, Ca-activated K channel (BK), and describes new evidence and theories regarding K secretory roles of BK in intercalated cells. Recent findings Isolated perfused tubule methods have revealed the importance of BK in flow-induced K secretion. Subsequently, mice with genetically deleted BK subunits revealed the complexities of BK-mediated K secretion. Deletion of BK alpha results in extreme aldosteronism, hypertension, and an absence of flow-induced K secretion. Deletion of the BK beta 1 ancillary subunit results in decreased handling of a K load, increased plasma K, mild aldosteronism and hypertension that is exacerbated by a high K diet. Deletion of BK beta 4 (beta 4KO) leads to insufficient K handling, high plasma K, fluid retention, but with milder hypertension. Fluid retention in beta 4KO may be the result of insufficient flow-induced secretion of adenosine triphosphate (ATP), which normally inhibits epithelial Na channels (ENaCs). Summary Classical physiological analysis of electrolyte handling in knockout mice has enlightened our understanding of the mechanism of handling K loads by renal K channels. Studies have focused on the different roles of BK-alpha/beta 1 and BK-alpha/beta 4 in the kidney. BK beta 1 hypertension may be a 'three-hit' hypertension, involving a K secretory defect, elevated production of aldosterone, and increased vascular tone. The disorders observed in BK knockout mice have shed new insights on the importance of proper renal K handling for maintaining volume balance and blood pressure.