Direct inhibition of basolateral K(ir)4.1/5.1 and K(ir)4.1 channels in the cortical collecting duct by dopamine

作者：Zaika Oleg L; Mamenko Mykola; Palygin Oleg; Boukelmoune Nabila; Staruschenko Alexander; Pochynyuk Oleh^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2013, 305(9): F1277-F1287.

DOI：10.1152/ajprenal.00363.2013

• basolateral potassium recycling
• dopamine receptors
• renal potassium
• channels
• distal nephron

It is recognized that dopamine promotes natriuresis by inhibiting multiple transporting systems in the proximal tubule. In contrast, less is known about the molecular targets of dopamine actions on water-electrolyte transport in the cortical collecting duct (CCD). Epithelial cells in the CCD are exposed to dopamine, which is synthesized locally or secreted from sympathetic nerve endings. Basolateral K+ channels in the distal renal tubule are critical for K+ recycling and controlling basolateral membrane potential to establish the driving force for Na+ reabsorption. Here, we demonstrate that K(ir)4.1 and K(ir)5.1 are highly expressed in the mouse kidney cortex and are localized to the basolateral membrane of the CCD. Using patch-clamp electrophysiology in freshly isolated CCDs, we detected highly abundant 40-pS and scarce 20-pS single channel conductances, most likely representing Kir4.1/5.1 and K(ir)4.1 channels, respectively. Dopamine reversibly decreased the open probability of both channels, with a relatively greater action on the K(ir)4.1/5.1 heterodimer. This effect was mediated by D2-like but not D1-like dopamine receptors. PKC blockade abolished the inhibition of basolateral K+ channels by dopamine. Importantly, dopamine significantly decreased the amplitude of K(ir)4.1/5.1 and K(ir)4.1 unitary currents. Consistently, dopamine induced an acute depolarization of basolateral membrane potential, as directly monitored using currentclamp mode in isolated CCDs. Therefore, we demonstrate that dopamine inhibits basolateral K(ir)4.1/5.1 and K(ir)4.1 channels in CCD cells via stimulation of D2-like receptors and subsequently PKC. This leads to depolarization of the basolateral membrane and a decreased driving force for Na+ reabsorption in the distal renal tubule.

• 出版日期2013-11