Coupled ATP and potassium efflux from intercalated cells

J. David Holtzclaw, Ryan J. Cornelius, Lori I. Hatcher, Steven C. Sansom

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Increased flow in the distal nephron induces K secretion through the large-conductance, calciumactivated 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/cm2) -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 P2 receptor blocker suramin or calciumfree 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.

Original languageEnglish (US)
Pages (from-to)F1319-F1326
JournalAmerican Journal of Physiology - Renal Physiology
Issue number6
StatePublished - Jun 2011


  • Collecting duct
  • Connexin
  • Distal nephron
  • MDCK-C11
  • Shear stress

ASJC Scopus subject areas

  • Physiology
  • Urology

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