Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Identification of a binding motif in the S5 helix that confers cholesterol-sensitivity to TRPV1.

Authors: Giovanni Picazo-Juarez, Silvina Romero-Suarez, Andrés Nieto-Posadas, Itzel Llorente, Andrés Jara-Oseguera, Margaret Briggs, Thomas J McIntosh, Sidney A Simon, Ernesto Ladron-de-Guevara, León D Islas, Tamara Rosenbaum

Journal, date & volume: , 2011 May 9 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21555515

Abstract
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-Ile(585) 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 membrane cholesterol content.