Dopamine inhibits basolateral potassium channels in the murine distal nephron

Abstract

It is recognized that dopamine promotes natriuresis by inhibiting NHE3 and Na+‐K+‐ATPase in the proximal tubule. In contrast, less is known about putative dopamine actions on the water‐electrolyte transport in the distal nephron. Basolateral side of the epithelial cells in the distal nephron is exposed to influence of dopamine secreted from sympathetic nerve endings. Furthermore, dopamine receptors are abundantly expressed at the basolateral membrane of the connecting tubule and the collecting duct cells. Basolateral K+ channels in the distal nephron are critical for potassium recycling and controlling basolateral membrane potential to promote electrogenic Na+ reabsorption. Using patch clamp electrophysiology in freshly isolated distal nephrons from mice, we detected ~20 pS and 40 pS basolateral K+ channels most likely representing Kir4.1, Kir4.1/5.1, respectively. Dopamine reversibly inhibited both channels when applied in a low micromolar range. Importantly, dopamine also decreased the amplitude of unitary currents approximately by 30% indicating depolarization of basolateral membrane and reduction of transepithelial voltage. We propose that consistently with its actions in the proximal tubule, dopamine reduces Na+ transport in the distal nephron, in part, by inhibiting basolateral K+ conductance and decreasing driving force for sodium reabsorption.