title: Involvement of phosphatidylinositol 4,5-bisphosphate in the desensitization of canonical transient receptor potential 5.
abstract: The classic transient receptor potential channel (TRPC) is a candidate for Ca(2+)-permeable cation channel in mammalian cells. TRPC5 is desensitized rapidly after activation by G protein-coupled receptor. Here we investigate the mechanisms of desensitization of TRPC5 using patch-clamp recording. TRPC5 was initially activated by muscarinic stimulation using 50 microM carbachol (CCh) and decayed rapidly in the presence of CCh (desensitization). Intracellularly-applied phosphatidylinositol 4,5-bisphosphate (PIP(2)) slowed the rate of desensitization. In contrast, several other phosphoinositides, including PI(3,4)P(2), PI(3,5)P(2), PI(3,4,5)P(3) and PI(4)P, had no effect on the desensitization of the TRPC5 current. This indicates that PIP(2) attenuates the desensitization of the TRPC5 current in a highly selective manner. Neither wortmannin, an inhibitor of phosphatidylinositol 4-kinase, or poly-L-lysine (PLL), a scavenger of PIP(2), had any effect on desensitization of the TRPC5 current. PIP(2) breakdown appears to be a required step in the desensitization of TRPC5 current, but PIP(2) depletion alone was insufficient for channel desensitization. TRPC5 was inhibited by cytochalasin D treatment. In mouse ileal myocytes, the desensitization of CCh-activated inward current (I(CCh)) also slowed in the presence of PIP(2) in recording pipettes. These results indicate that PIP(2) is involved in the desensitization of TRPC5 currents.
authors.affiliation: Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
authors.forename: Min Tae
authors.initials: MT
authors.lastname: Kim
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Seon Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Insuk
authors.initials: I
authors.lastname: So