Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in renal proximal tubule cells from rat models of hypertension: Aged F344 rats and spontaneously hypertensive rats

Michelle T. Barati, Corey J. Ketchem, Michael L. Merchant, Walter B. Kusiak, Pedro A. Jose, Edward J. Weinman, Amanda J. LeBlanc, Eleanor D. Lederer, Syed J. Khundmiri

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Dopamine decreases Na-KATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodiumhydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells, dopamine decreases NHERF-1 association with NKA 1 but increases its association with D1R. However, it is not known whether NHERF-1 plays a role in dopamine-mediated NKA regulation in animal models of hypertension. We hypothesized that defective dopamine-mediated regulation of NKA results from the decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls, normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated phosphorylation of NKA, and ouabain-inhibitable K+ transport are reduced. Transfection of NHERF-1 into PTCs from aged F344 and SHRs restored dopamine-mediated inhibition of NKA. These results suggest that decreased renal NHERF-1 expression contributes to the impaired dopamine-mediated inhibition of NKA in PTCs from animal models of hypertension.

Original languageEnglish (US)
Pages (from-to)C197-C206
JournalAmerican Journal of Physiology - Cell Physiology
Volume313
Issue number2
DOIs
StatePublished - Aug 3 2017
Externally publishedYes

Keywords

  • Dopamine
  • F344
  • Hypertension
  • NHERF-1
  • Na-K-ATPase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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