title: Direct inhibition of basolateral Kir4.1/5.1 and Kir4.1 channels in the cortical collecting duct by dopamine.
abstract: 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 Kir4.1 and Kir5.1 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 Kir4.1 channels, respectively. Dopamine reversibly decreased the open probability of both channels, with a relatively greater action on the Kir4.1/5.1 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 Kir4.1/5.1 and Kir4.1 unitary currents. Consistently, dopamine induced an acute depolarization of basolateral membrane potential, as directly monitored using current-clamp mode in isolated CCDs. Therefore, we demonstrate that dopamine inhibits basolateral Kir4.1/5.1 and Kir4.1 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.
authors.affiliation: Dept. of Integrative Biology and Pharmacology, Univ. of Texas Health Science Center, 6431 Fannin St., Houston, TX 77030. Oleh.M.Pochynyuk@uth.tmc.edu.
authors.forename: Oleg L
authors.initials: OL
authors.lastname: Zaika
authors.forename: Mykola
authors.initials: M
authors.lastname: Mamenko
authors.forename: Oleg
authors.initials: O
authors.lastname: Palygin
authors.forename: Nabila
authors.initials: N
authors.lastname: Boukelmoune
authors.forename: Alexander
authors.initials: A
authors.lastname: Staruschenko
authors.forename: Oleh
authors.initials: O
authors.lastname: Pochynyuk
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D000097062:Kir5.1 Channel; D000098854:Kcnj10 Channel
chemical_list: D004298:Dopamine; D024661:Potassium Channels, Inwardly Rectifying; D011493:Protein Kinase C; D017448:Receptors, Dopamine D2; D012964:Sodium; D000097062:Kir5.1 Channel; D000098854:Kcnj10 Channel
keywords: basolateral potassium recycling; distal nephron; dopamine receptors; renal potassium channels