Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Regular Articles
Involvement of Phosphatidylinositol 4,5-Bisphosphate in the Desensitization of Canonical Transient Receptor Potential 5
Byung Joo KimMin Tae KimJu-Hong JeonSeon Jeong KimInsuk So
ジャーナル フリー

2008 年 31 巻 9 号 p. 1733-1738


The classic transient receptor potential channel (TRPC) is a candidate for Ca2+-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 μM carbachol (CCh) and decayed rapidly in the presence of CCh (desensitization). Intracellularly-applied phosphatidylinositol 4,5-bisphosphate (PIP2) slowed the rate of desensitization. In contrast, several other phosphoinositides, including PI(3,4)P2, PI(3,5)P2, PI(3,4,5)P3 and PI(4)P, had no effect on the desensitization of the TRPC5 current. This indicates that PIP2 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 PIP2, had any effect on desensitization of the TRPC5 current. PIP2 breakdown appears to be a required step in the desensitization of TRPC5 current, but PIP2 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 (ICCh) also slowed in the presence of PIP2 in recording pipettes. These results indicate that PIP2 is involved in the desensitization of TRPC5 currents.

© 2008 The Pharmaceutical Society of Japan
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