Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 289, Issue 3, Pages C591-C600Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00440.2004
Keywords
nonselective cation channels; Ca2(+) -permeable cation channels
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The classic type of transient receptor potential channel ( TRPC) is a molecular candidate for Ca2+-permeable cation channel in mammalian cells. TRPC5 is desensitized rapidly after activation by G protein-coupled receptor. Herein we report our investigation into the desensitization of mTRPC5 and localization of the molecular determinants of this desensitization using mutagenesis. TRPC5 was initially activated by muscarinic stimulation using 100 mu M carbachol (CCh) and then decayed rapidly even in the presence of CCh ( desensitization). Increased EGTA or omission of MgATP in the pipette solution slowed the rate of this desensitization. The protein kinase C (PKC) inhibitors, 1 mu M chelerythrine, 100 nM GF109203X, or PKC peptide inhibitor (19 - 36), inhibited this desensitization of TRPC5 activated by 100 mu M CCh. When TRPC5 current was activated by intracellular GTP gamma S, PKC inhibitors prevented TRPC5 desensitization and the mutation of TRPC5 T972 to alanine slowed the desensitization process dramatically. We conclude that the desensitization of TRPC5 occurs via PKC phosphorylation and suggest that threonine at residue 972 of mouse TRPC5 might be required for its phosphorylation by PKC.
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