title: Coupled ATP and potassium efflux from intercalated cells.
abstract: 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 (τ; 10 dynes/cm(2)) -induced, BK-dependent, K efflux. We found that 10 μM 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 τ-induced K efflux, suggesting that K efflux is at least partially dependent on purinergic signaling. BK-β4 small interfering (si) RNA, but not nontarget siRNA, decreased ATP secretion and both ATP-dependent and τ-induced K efflux. Similarly, carbenoxolone (25 μM), which blocks connexins, putative ATP pathways, blocked τ-induced K efflux and ATP secretion. Compared with BK-β4(-/-) 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 τ-induced ATP release in IC.
authors: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
authors: J David
authors: JD
authors: Holtzclaw
authors: Ryan J
authors: RJ
authors: Cornelius
authors: Lori I
authors: LI
authors: Hatcher
authors: Steven C
authors: SC
authors: Sansom
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009399:Nephrons / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D018709:Statistics, Nonparametric
chemical_list: D024681:Potassium Channels, Calcium-Activated; D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium