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

doi:10.1016/j.bbamcr.2013.08.017

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

Journal article

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

Seung-Kuy Cha, Ji-Hee Kim and Chou-Long Huang

Biochimica et biophysica acta. Molecular cell research, Vol.1833(12), pp.3046-3053

12/2013

DOI: 10.1016/j.bbamcr.2013.08.017

PMID: 24001793

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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. •TRPV5 and TRPV6 channels are activated by shear force generated by fluid flow.•Flow-mediated Ca2+ entry via TRPV5 and 6 can activate Slo1 Ca2+-activated K+ channels.•Flow stimulation of TRPV5 involves N-glycan of the channel.

Flow-mediated Ca2 + entry

Flow-mediated K+ secretion

TRPV6

Ca2 +-activated K+ channel

ROMK

TRPV5

Details

Title: Subtitle: Flow-induced activation of TRPV5 and TRPV6 channels stimulates Ca2+-activated K+ channel causing membrane hyperpolarization
Creators: Seung-Kuy Cha - Department of Physiology, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
Ji-Hee Kim - Department of Physiology, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
Chou-Long Huang - Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
Resource Type: Journal article
Publication Details: Biochimica et biophysica acta. Molecular cell research, Vol.1833(12), pp.3046-3053
DOI: 10.1016/j.bbamcr.2013.08.017
PMID: 24001793
NLM abbreviation: Biochim Biophys Acta Mol Cell Res
ISSN: 0167-4889
eISSN: 1879-2596
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/501100004085, name: Ministry of Education, Science and Technology, award: 2010-0024789; DOI: 10.13039/501100008005, name: Yonsei University College of Medicine, award: YUWCM-2010-7-0482; DOI: 10.13039/100000002, name: National Institutes of Health, award: DK-85726; DOI: 10.13039/501100003725, name: National Research Foundation of Korea
Language: English
Date published: 12/2013
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984094589402771

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