Flow-induced activation of TRPV5 and TRPV6 channels stimulates Ca 2+ -activated K + channel causing membrane hyperpolarization

Seungkuy Cha, Ji Hee Kim, Chou Long Huang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

TRPV5 and TRPV6 channels are expressed in distal renal tubules and play important roles in the transcellular Ca 2+ reabsorption in kidney. They are regulated by multiple intracellular factors including protein kinases A and C, membrane phospholipid PIP 2 , protons, and divalent ions Ca 2+ and Mg 2+ . 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 Ca 2+ entry and increased intracellular Ca 2+ 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 La 3+ . 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
Pages (from-to)3046-3053
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number12
DOIs
Publication statusPublished - 2013 Dec 1

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Distal Kidney Tubule
Ion Channels
Large-Conductance Calcium-Activated Potassium Channels
Membranes
Thiazides
Cyclic AMP-Dependent Protein Kinases
Glycosylation
Protein Kinase C
Protons
Phospholipids
Ions
Kidney
TRPV6 channel

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "TRPV5 and TRPV6 channels are expressed in distal renal tubules and play important roles in the transcellular Ca 2+ reabsorption in kidney. They are regulated by multiple intracellular factors including protein kinases A and C, membrane phospholipid PIP 2 , protons, and divalent ions Ca 2+ and Mg 2+ . 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 Ca 2+ entry and increased intracellular Ca 2+ 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 La 3+ . 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.",
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Flow-induced activation of TRPV5 and TRPV6 channels stimulates Ca 2+ -activated K + channel causing membrane hyperpolarization . / Cha, Seungkuy; Kim, Ji Hee; Huang, Chou Long.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1833, No. 12, 01.12.2013, p. 3046-3053.

Research output: Contribution to journalArticle

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