Coupled ATP and potassium efflux from intercalated cells.
J David Holtzclaw1, Ryan J Cornelius, Lori I Hatcher
1Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
American Journal of Physiology. Renal Physiology
|April 2, 2011
Summary
Increased distal nephron flow stimulates potassium (K) secretion via BK channels in intercalated cells (IC). Purinergic signaling, involving ATP release, plays a key role in this flow-induced K efflux.
Area of Science:
- Nephrology
- Cell Physiology
- Ion Transport
Background:
- Distal nephron flow increases potassium (K) secretion via large-conductance, calcium-activated K channels (BK).
- Intercalated cells (IC) express BK channels and release ATP in response to flow.
- Purinergic signaling, mediated by ATP, is hypothesized to be involved in flow-induced K secretion.
Purpose of the Study:
- To investigate the role of purinergic signaling in shear stress-induced, BK-dependent K efflux from IC.
- To elucidate the relationship between ATP release and K secretion in response to flow.
Main Methods:
- Utilized shear stress (τ) to stimulate IC.
- Measured intracellular calcium (Ca) concentration, K efflux, and ATP secretion.
- Employed P2 receptor blocker (suramin), calcium-free buffer, BK-β4 siRNA, and carbenoxolone (connexin blocker).
- Compared urinary ATP excretion in wild-type and BK-β4(-/-) mice under high flow conditions.
Main Results:
- ATP increased IC Ca concentration and induced BK-dependent K efflux and IC volume decrease.
- Suramin and carbenoxolone inhibited τ-induced K efflux and ATP secretion.
- BK-β4 siRNA reduced ATP secretion and both ATP-dependent and τ-induced K efflux.
- Wild-type mice with high distal flows showed greater urinary ATP excretion than BK-β4(-/-) mice.
Conclusions:
- Purinergic signaling is involved in shear stress-induced K efflux from IC.
- Coupled electrochemical efflux of K and ATP is a mechanism for τ-induced ATP release in IC.
- BK-β4 subunit is crucial for ATP secretion and K efflux in response to flow.
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