Coupled ATP and potassium efflux from intercalated cells
| Autor: | Steven C. Sansom, Ryan J. Cornelius, Lori Hatcher, J. David Holtzclaw |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Physiology
Potassium Blotting Western chemistry.chemical_element Connexin Nephron Calcium Statistics Nonparametric chemistry.chemical_compound Mice Potassium Channels Calcium-Activated Adenosine Triphosphate medicine Animals Intercalated Cell RNA Small Interfering Mice Knockout Kidney Chemistry Articles Nephrons Immunohistochemistry medicine.anatomical_structure Biochemistry Biophysics Efflux Adenosine triphosphate |
| Popis: | 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/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 P2receptor 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. |
| Databáze: | OpenAIRE |
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