IGF‐1 acutely increases activity of basolateral ClC‐K2‐like Cl‐ channels in the distal nephron (892.12)

Abstract

Insulin growth factor 1 (IGF‐1) is known to promote anti‐natriuresis by stimulating ENaC‐mediated sodium reabsorption in the distal renal tubule. However, it remains unclear whether IGF‐1 also augments Cl‐ transport at this place. Using patch clamp electrophysiology in freshly isolated mouse distal nephrons we detected highly abundant single channel conductance of approximately 14 pS in a cell‐attached configuration. Decreased Cl‐ concentration in the pipette resulted in a rightward shift of I‐V relation, indicating Cl‐ selectivity of the recorded channel. The single channel properties of the recorded channel are comparable with ClC‐K2 that was reported to be functionally expressed predominantly in the intercalated cells of distal nephron. In tandem with apically localized pendrin, ClC‐K2 is thought to contribute to distal nephron Cl‐ absorption. We found that acute application of 100 nM IGF‐1 significantly increases open probability of the ClC‐K2‐like channel in a reversible manner. Pretreatment of distal nephrons with a selective PI3‐kinase inhibitor LY292002 abolished activation of the channel by IGF‐1. We propose that, concomitantly with its stimulatory effects on sodium transport, IGF‐1 also favors distal nephron Cl‐ absorption by increasing activity of basolateral ClC‐K2‐like channels in a PI3‐K‐dependent manner.Grant Funding Source: DK095029