The role of the BK channel in potassium homeostasis and flow-induced renal potassium excretion

The kidney is the major regulator of potassium homeostasis. In addition to the ROMK channels, large conductance Ca2+-activated K+ (BK) channels are expressed in the apical membrane of the aldosterone sensitive distal nephron where they could contribute to renal K+ secretion. We studied flow-induced K+ secretion in BK channel α-subunit knockout (BK−/−) mice by acute pharmacologic blockade of vasopressin V2 receptors, which caused similar diuresis in wild-type and knockout mice. However, wild-type mice, unlike the BK−/−, had a concomitant increase in urinary K+ excretion and a significant correlation between urinary flow rate and K+ excretion. Both genotypes excreted similar urinary amounts of K+ irrespective of K+ diet. This was associated, however, with higher plasma aldosterone and stronger expression of ROMK in the apical membrane of the aldosterone-sensitive portions of the distal nephron in the knockout than in the wild-type under control diet and even more so with the high-K+ diet. High-K+ intake significantly increased the renal expression of the BK channel in the wild-type mouse. Finally, despite the higher plasma K+ and aldosterone levels, BK−/− mice restrict urinary K+ excretion when placed on a low-K+ diet to the same extent as the wild-type. These studies suggest a role of the BK channel α-subunit in flow-induced K+ secretion and in K+ homeostasis. Higher aldosterone and an upregulation of ROMK may compensate for the absence of functional BK channels.