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Am J Physiol Renal Physiol 290: F117-F126, 2006. First published August 9, 2005; doi:10.1152/ajprenal.00143.2005
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Regulation of TRPV1 by a novel renally expressed rat TRPV1 splice variant

Wei Tian,1 Yi Fu,1 Donna H. Wang,2 and David M. Cohen1

1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University and the Portland Veterans Affairs Medical Center, Portland, Oregon; and 2Department of Medicine and Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan

Submitted 6 April 2005 ; accepted in final form 3 August 2005

The capsaicin receptor and transient receptor potential channel TRPV1 senses heat, protons, and vanilloid agonists in peripheral sensory ganglia. Abundant data have suggested the presence of potentially novel splice variants in the kidney. We report a novel rat TRPV1 splice variant, TRPV1VAR, cloned from kidney papilla. TRPV1VAR cDNA was identified in multiple kidney tissues. Its sequence was fully compatible with potential splice donor and acceptor sites in the rat TRPV1 gene. TRPV1VAR is predicted to encode a truncated form of TRPV1 consisting of the NH2-terminal 248 residues of TRPV1 (all within the NH2-terminal intracellular domain) followed by five nonconsensus amino acids (Arg-Glu-Ala-Met-Trp) and a stop codon. The variant utilizes the same consensus Kozak sequence as canonical TRPV1. A band of the appropriate molecular mass was identified in rat kidney papillary (but not medullary) lysates immunoblotted with an antibody directed against the NH2 terminus of TRPV1, whereas an antibody recognizing the TRPV1 COOH terminus failed to detect it. Upon heterologous expression in HEK 293 cells, TRPV1VAR potentiated the ability of cotransfected TRPV1 to confer calcium influx in response to resiniferatoxin. TRPV1VAR did not influence expression or cell surface localization of cotransfected TRPV1. TRPV1VAR protein product associated with the NH2 terminus of canonical TRPV1. Interestingly, when expressed in the COS-7 epithelial cell line, TRPV1VAR functioned in a dominant-negative acting capacity, partially blocking TRPV1-dependent resiniferatoxin responsiveness. We conclude that TRPV1VAR is one of perhaps several TRPV1 splice variants expressed in rat kidney and that it may serve to modulate TRPV1 responsiveness in some tissues.

transient receptor potential channel



Address for reprint requests and other correspondence: D. M. Cohen, Mailcode PP262, Oregon Health & Science Univ., 3314 S.W. US Veterans Hospital Rd., Portland, OR 97239 (e-mail: cohend{at}ohsu.edu)




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