Coupled ATP and potassium efflux from intercalated cells

Holtzclaw JD, Cornelius RJ, Hatcher LI, Sansom SC. Coupled ATP and potassium efflux from intercalated cells. Am J Physiol Renal Physiol 300: F1319-F1326, 2011. First published March 30, 2011; doi:10.1152/ajprenal.00112.2011.-Increased flow in the distal nephron induces K secretion through the large-conductance, calcium-activated K channel (BK), which is primarily expressed in intercalated cells (IC). Since flow also increases ATP release from IC, we hypothesized that purinergic signaling has a role in shear stress (tau; 10 dynes/cm(2))-induced, BK-dependent, K efflux. We found that 10 mu M ATP led to increased IC Ca concentration, which was significantly reduced in the presence of the P(2) receptor blocker suramin or calcium-free buffer. ATP also produced BK-dependent K efflux, and IC volume decrease. Suramin inhibited tau-induced K efflux, suggesting that K efflux is at least partially dependent on purinergic signaling. BK-beta 4 small interfering (si) RNA, but not nontarget siRNA, decreased ATP secretion and both ATP-dependent and tau-induced K efflux. Similarly, carbenoxolone (25 mu M), which blocks connexins, putative ATP pathways, blocked tau-induced K efflux and ATP secretion. Compared with BK-beta 4(-/-) mice, wild-type mice with high distal flows exhibited significantly more urinary ATP excretion. These data demonstrate coupled electrochemical efflux between K and ATP as part of the mechanism for tau-induced ATP release in IC.