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

Biochim Biophys Acta. 2013 Dec;1833(12):3046-3053. doi: 10.1016/j.bbamcr.2013.08.017. Epub 2013 Aug 31.


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 PIP2, 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.

Keywords: Ca(2+)-activated K(+) channel; Flow-mediated Ca(2+) entry; Flow-mediated K(+) secretion; ROMK; TRPV5; TRPV6.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Glycosylation
  • HEK293 Cells
  • Humans
  • Ion Channel Gating*
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Membrane Potentials*
  • Potassium Channels, Calcium-Activated / metabolism*
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Rheology*
  • Stress, Mechanical
  • TRPV Cation Channels / metabolism*


  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Potassium Channels, Inwardly Rectifying
  • TRPV Cation Channels
  • TRPV6 channel
  • Calcium