Complex regulation of TRPM8 channel

• 作 者: BidauxG;GordienkoD;GkikaD;LemonnierL;SkrymaR;PrevarskayaN;
• 机 构: Laboratory of Cell Physiology,1NSERM U1003,University of Lille 1,FRANCE
• 出 处: The 3rd Ion Channel Conference: Ion channels-Structure, Func
• 发表日期: 2011年期

　　Transient Receptor Potential, Melastatine member 8 channel (TRPM8) represents an ion channel activated by cold and cooling agents like menthol that underlies the cold-induced excitation of sensory neurons.Interestingly, the only human tissue outside the peripheral nervous system, in which the expression of TRPM8 transcripts was detected at high levels, was prostate-a tissue not exposed to any essential temperature variations.We show that the TRPMg cloned from human prostate and heterologously expressed in HEK293 cells is regulated by a number of intracellular messengers such as cAMP, lysophospholipids (LPLs), arachidonic acid and Ca2+.Further, we report the cloning from prostate cancer cells of new short-splice variants of TRPM8, termed short TRPM8α (sTRPM8α) and short TRPM8β (sTRPM8β) and show that both variants associate with the C-terminal tail of the full-size TRPM8 channel, resulting in stabilization of its closed state and thus reducing both its cold sensitivity and its activity.Our findings, therefore, uncover a new mode of the regulation of TRPM8 channel by its splice variants.