Involvement of Phosphatidylinositol 4,5-Bisphosphate in the Desensitization of Canonical Transient Receptor Potential 5(Highlighted paper selected by Editor-in-chief,Pharmacology)

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概要

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• 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 50μM 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. PIP2 breakdown appears to be a required step in the desensitization of TRPC5 current, but PIP_2 depletion alone was insufficient for channel desensitization. TRPCS 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.

• 公益社団法人日本薬学会の論文
• 2008-09-01

著者

• So Insuk

  Dep. Of Physiology Seoul National Univ. Coll. Of Medicine

• Kim Seon

  Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University

• KIM Byung

  Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of

• JEON Ju-Hong

  Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of

• SO Insuk

  Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of

• Kim Byung

  Div. Of Longevity And Biofunctional Medicine Pusan National Univ. School Of Korean Medicine

• Kim Seon

  Center For Bio-artificial Muscle And Dep. Of Biomedical Engineering Hanyang Univ.

• Jeon Ju-hong

  Dep. Of Physiology Seoul National Univ. Coll. Of Medicine

• KIM Min

  Center for Bio-Artificial Muscle and Department of Physiology, Seoul National University College of

• Kim Min

  Center For Bio-artificial Muscle And Department Of Physiology Seoul National University College Of M

関連論文

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• Suppression of transient receptor potential melastatin 7 channel induces cell death in gastric cancer
• Inhibition of Aldose Reductase by Phenylethanoid Glycoside Isolated from the Seeds of Paulownia coreana
• Involvement of Phosphatidylinositol 4,5-Bisphosphate in the Desensitization of Canonical Transient Receptor Potential 5(Highlighted paper selected by Editor-in-chief,Pharmacology)
• Melastatin-Type transient receptor potential channel 7 is required for intestinal pacemaking activity(Kuriyama Hirosi Award,Program and Abstracts of Papers for 48th Annual Meeting of The Japan Society of Smooth Muscle Research)
• The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract

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