Affiliation:
1. Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas
Abstract
Adenosine plays an important role in various aspects of kidney physiology, but the specific targets and mechanisms of actions are not completely understood. The collecting duct has the highest expression of adenosine receptors, particularly adenosine A1receptors (A1Rs). Interstitial adenosine levels are greatly increased up to a micromolar range in response to dietary salt loading. We have previously shown that the basolateral membrane of principal cells has primarily K+conductance mediated by Kir4.1/5.1 channels to mediate K+recycling and to set up a favorable driving force for Na+/K+exchange ( 47 ). Intercalated cells express the Cl−ClC-K2/b channel mediating transcellular Cl−reabsorption. Using patch-clamp electrophysiology in freshly isolated mouse collecting ducts, we found that acute application of adenosine reversely inhibits ClC-K2/b open probability from 0.31 ± 0.04 to 0.17 ± 0.06 and to 0.10 ± 0.05 for 1 and 10 µM, respectively. In contrast, adenosine (10 µM) had no measureable effect on Kir4.1/5.1 channel activity in principal cells. The inhibitory effect of adenosine on ClC-K2/b was abolished in the presence of the A1R blocker 8-cyclopentyl-1,3-dipropylxanthine (10 µM). Consistently, application of the A1R agonist N6-cyclohexyladenosine (1 µM) recapitulated the inhibitory action of adenosine on ClC-K2/b open probability. The effects of adenosine signaling in the collecting duct were independent from its purinergic counterpartner, ATP, having no measurable actions on ClC-K2/b and Kir4.1/5.1. Overall, we demonstrated that adenosine selectively inhibits ClC-K2/b activity in intercalated cells by targeting A1Rs. We propose that inhibition of transcellular Cl−reabsorption in the collecting duct by adenosine would aid in augmenting NaCl excretion during high salt intake.
Funder
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
American Heart Association
Publisher
American Physiological Society
Cited by
3 articles.
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