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标题：Involvement of Phosphatidylinositol 4,5-Bisphosphate in the Desensitization of Canonical Transient Receptor Potential 5
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作者：Byung Joo Kim ; Min Tae Kim ; Ju-Hong Jeon 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：9
页码：1733-1738
DOI：10.1248/bpb.31.1733
出版社：The Pharmaceutical Society of Japan
摘要：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 μ M 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 ( I _CCh) also slowed in the presence of PIP₂ in recording pipettes. These results indicate that PIP₂ is involved in the desensitization of TRPC5 currents.
关键词：canonical transient receptor potential 5;muscarinic stimulation;phosphatidylinositol 4,5-bisphosphate