Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8303914 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2013 | 8 Pages |
Abstract
TRPV5 and TRPV6 channels are expressed in distal renal tubules and play important roles in the transcellular Ca2Â + reabsorption in kidney. They are regulated by multiple intracellular factors including protein kinases A and C, membrane phospholipid PIP2, protons, and divalent ions Ca2Â + and Mg2Â +. 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 2Â min. Fluid flow stimulated TRPV5 and 6-mediated Ca2Â + entry and increased intracellular Ca2Â + 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 La3Â +. 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.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Seung-Kuy Cha, Ji-Hee Kim, Chou-Long Huang,