| Identification of a binding motif in the S5 helix that confers cholesterol-sensitivity to TRPV1. | |
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MedLine Citation:
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PMID: 21555515 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The TRPV1 ion channel serves as an integrator of noxious stimuli with its activation linked to pain and neurogenic inflammation. Cholesterol, a major component of cell membranes, modifies the function of several types of ion channels. Here, using measurements of capsaicin-activated currents in excised-patches from TRPV1-expressing HEK cells, we show that enrichment with cholesterol, but not its diastereoisomer epicholesterol, markedly decreased wild-type rat TRPV1 currents. Substitutions in the S5 helix, rTRPV1-R579D and rTRPV1-F582Q, decreased this cholesterol response and rTRPV1-L585I was insensitive to cholesterol addition. Two human TRPV1 variants, with different amino acids at position 585, had different responses to cholesterol with hTRPV1-I585 being insensitive to this molecule. However, hTRPV1-I585L was inhibited by cholesterol addition similar to rTRPV1 with the same S5 sequence. In the absence of capsaicin, cholesterol enrichment also inhibited TRPV1 currents induced by elevated temperature and voltage. These data suggest that there is a cholesterol-binding site in TRPV1 and that the functions of TRPV1 depend on the genetic variant and on membrane cholesterol content. |
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Authors:
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Giovanni Picazo-Juarez; Silvina Romero-Suarez; Andres Nieto-Posadas; Itzel Llorente; Andres Jara-Oseguera; Margaret Briggs; Thomas J McIntosh; Sidney A Simon; Ernesto Ladron-de-Guevara; Leon D Islas; Tamara Rosenbaum |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-9 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Universidad Nacional Autonoma de Mexico, Mexico; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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