Hills, Claire E., Bland, Rosemary and Squires, Paul E.. (2012) Functional expression of TRPV4 channels in human collecting duct cells : implications for secondary hypertension in diabetic nephropathy. Experimental Diabetes Research, 2012 . p. 936518. ISSN 1687-5214

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Abstract

Background. The Vanilloid subfamily of transient receptor potential (TRPV) ion channels has been widely implicated in detecting osmotic and mechanical stress. In the current study, we examine the functional expression of TRPV4 channels in cell volume regulation in cells of the human collecting duct. Methods. Western blot analysis, siRNA knockdown, and microfluorimetry were used to assess the expression and function of TRPV4 in mediating Ca2+-dependent mechanical stimulation within a novel system of the human collecting duct (HCD). Results. Native and siRNA knockdown of TRPV4 protein expression was confirmed by western blot analysis. Touch was used as a cell-directed surrogate for osmotic stress. Mechanical stimulation of HCD cells evoked a transient increase in [Ca2+]i that was dependent upon thapsigargin-sensitive store release and Ca2+ influx. At 48 hrs, high glucose and mannitol (25 mM) reduced TRPV4 expression by 54% and 24%, respectively. Similar treatment doubled SGK1 expression. Touch-evoked changes were negated following TRPV4 knockdown. Conclusion. Our data confirm expression of Ca2+-dependent TRPV4 channels in HCD cells and suggest that a loss of expression in response to high glucose attenuates the ability of the collecting duct to exhibit regulatory volume decreases, an effect that may contribute to the pathology of fluid and electrolyte imbalance as observed in diabetic nephropathy.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Medicine > Warwick Medical School > Education Development and Research Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	TRP channels, Kidneys -- Physiology
Journal or Publication Title:	Experimental Diabetes Research
Publisher:	Hindawi Publishing Corporation
ISSN:	1687-5214
Date:	2012
Volume:	2012
Page Range:	p. 936518
Identification Number:	10.1155/2012/936518
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	University of Warwick, Medical Research Council (Great Britain) (MRC)
Grant number:	G4500017 (MRC)
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URI:	http://wrap.warwick.ac.uk/id/eprint/50055

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