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.
|Number of pages||8|
|Journal||Biochimica et Biophysica Acta - Molecular Cell Research|
|Publication status||Published - 2013 Dec|
Bibliographical noteFunding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (Grant 2010-0024789 to S.-K. C.), a research grant from the Yonsei University Wonju College of Medicine (Grant YUWCM-2010-7-0482 to S.-K.C.), and the National Institutes of Health of USA ( DK-85726 to C.-L.H). C.-L.H holds the Jacob Lemann Professorship in Calcium Transport of University of Texas Southwestern Medical Center. We thank Dr Chul-Seung Park for Slo1 plasmid.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology