Role of collecting duct principal cell NOS1β in sodium and potassium homeostasis

Kelly A. Hyndman, Elena Isaeva, Oleg Palygin, Luciano D. Mendoza, Aylin R. Rodan, Alexander Staruschenko, Jennifer S. Pollock

Research output: Contribution to journalArticlepeer-review

Abstract

The nitric oxide (NO)-generating enzyme, NO synthase-1β (NOS1β), is essential for sodium (Na+) homeostasis and blood pressure control. We previously showed that collecting duct principal cell NOS1β is critical for inhibition of the epithelial sodium channel (ENaC) during high Na+ intake. Previous studies on freshly isolated cortical collecting ducts (CCD) demonstrated that exogenous NO promotes basolateral potassium (K+) conductance through basolateral channels, presumably Kir4.1 (Kcnj10) and Kir5.1 (Kcnj16). We, therefore, investigated the effects of NOS1β knockout on Kir4.1/Kir5.1 channel activity. Indeed, in CHO cells overexpressing NOS1β and Kir4.1/Kir5.1, the inhibition of NO signaling decreased channel activity. Male littermate control and principal cell NOS1β knockout mice (CDNOS1KO) on a 7-day, 4% NaCl diet (HSD) were used to detect changes in basolateral K+ conductance. We previously demonstrated that CDNOS1KO mice have high circulating aldosterone despite a high-salt diet and appropriately suppressed renin. We observed greater Kir4.1 cortical abundance and significantly greater Kir4.1/Kir5.1 single-channel activity in the principal cells from CDNOS1KO mice. Moreover, blocking aldosterone action with in vivo spironolactone treatment resulted in lower Kir4.1 abundance and greater plasma K+ in the CDNOS1KO mice compared to controls. Lowering K+ content in the HSD prevented the high aldosterone and greater plasma Na+ of CDNOS1KO mice and normalized Kir4.1 abundance. We conclude that during chronic HSD, lack of NOS1β leads to increased plasma K+, enhanced circulating aldosterone, and activation of ENaC and Kir4.1/Kir5.1 channels. Thus, principal cell NOS1β is required for the regulation of both Na+ and K+ by the kidney.

Original languageEnglish (US)
Article numbere15080
JournalPhysiological Reports
Volume9
Issue number20
DOIs
StatePublished - Oct 2021

Keywords

  • collecting duct
  • high salt
  • K channels
  • Kcnj10
  • Kcnj16
  • kidney
  • nitric oxide
  • NOS1β
  • potassium

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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