Flow-induced activation of TRPV5 and TRPV6 channels stimulates Ca2+-activated K+ channel causing membrane hyperpolarization

Seung Kuy Cha, Ji Hee Kim, Chou Long Huang

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

TRPV5 and TRPV6 channels are expressed in distal renal tubules and play important roles in the transcellular Ca2+ reabsorption in kidney. They are regulated by multiple intracellular factors including protein kinases A and C, membrane phospholipid PIP2, protons, and divalent ions Ca2+ and Mg2+. Here, we report that fluid flow that generates shear force within the physiological range of distal tubular fluid flow activated TRPV5 and TRPV6 channels expressed in HEK cells. Flow-induced activation of channel activity was reversible and did not desensitize over 2min. Fluid flow stimulated TRPV5 and 6-mediated Ca2+ entry and increased intracellular Ca2+ concentration. N-glycosylation-deficient TRPV5 channel was relatively insensitive to fluid flow. In cells coexpressing TRPV5 (or TRPV6) and Slo1-encoded maxi-K channels, fluid flow induced membrane hyperpolarization, which could be prevented by the maxi-K blocker iberiotoxin or TRPV5 and 6 blocker La3+. In contrast, fluid flow did not cause membrane hyperpolarization in cells coexpressing ROMK1 and TRPV5 or 6 channel. These results reveal a new mechanism for the regulation of TRPV5 and TRPV6 channels. Activation of TRPV5 and TRPV6 by fluid flow may play a role in the regulation of flow-stimulated K+ secretion via maxi-K channels in distal renal tubules and in the mechanism of pathogenesis of thiazide-induced hypocalciuria.

Original languageEnglish (US)
Pages (from-to)3046-3053
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • Ca-activated K channel
  • Flow-mediated Ca entry
  • Flow-mediated K secretion
  • ROMK
  • TRPV5
  • TRPV6

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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