Intracellular spermine blocks TRPC4 channel via electrostatic interaction with C-terminal negative amino acids
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  • 作者:Jinsung Kim ; Sang Hui Moon ; Young-Cheul Shin…
  • 关键词:TRPC4 ; NSCC ; GI physiology ; Polyamine ; Spermine
  • 刊名:Pfl¨¹gers Archiv - European Journal of Physiology
  • 出版年:2016
  • 出版时间:April 2016
  • 年:2016
  • 卷:468
  • 期:4
  • 页码:551-561
  • 全文大小:1,143 KB
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  • 作者单位:Jinsung Kim (1) (2)
    Sang Hui Moon (3)
    Young-Cheul Shin (2)
    Ju-Hong Jeon (2)
    Kyu Joo Park (3)
    Kyu Pil Lee (4)
    Insuk So (2)

    1. College of Medicine, Catholic University of Korea, Seoul, 137-701, Republic of Korea
    2. Department of Physiology, College of Medicine, Seoul National University, Seoul, 110-799, Republic of Korea
    3. Department of Surgery, College of Medicine, Seoul National University, Seoul, 110-799, Republic of Korea
    4. Department of Physiology, College of Veterinary Medicine, Chungnam National University, Daejeon, 305-764, Republic of Korea
  • 刊物主题:Human Physiology;
  • 出版者:Springer Berlin Heidelberg
  • ISSN:1432-2013
文摘
Transient receptor potential canonical (TRPC) 4 channels are calcium-permeable, nonselective cation channels and are widely expressed in mammalian tissue, especially in the GI tract and brain. TRPC4 channels are known to be involved in neurogenic contraction of ileal smooth muscle cells via generating cationic current after muscarinic stimulation (muscarinic cationic current (mI<sub>catsub>)). Polyamines exist in numerous tissues and are believed to be involved in cell proliferation, differentiation, scar formation, wound healing, and carcinogenesis. Besides, physiological polyamines are essential to maintain inward rectification of cardiac potassium channels (Kir<sub>2.1sub>). At membrane potentials more positive than equilibrium potential, intracellular polyamines plug the cytosolic surface of the Kir<sub>2.1sub> so that potassium ions cannot pass through the pore. Recently, it was reported that polyamines inhibit not only cardiac potassium channels but also nonselective cation channels that mediate the generation of mI<sub>catsub>. Here, we report that TRPC4, a definite mI<sub>catsub> mediator, is inhibited by intracellular spermine with great extent. The inhibition was specific to TRPC4 and TRPC5 channels but was not effective to TRPC1/4, TRPC1/5, and TRPC3 channels. For this inhibition to occur, we found that glutamates at 728th and 729th position of TRPC4 channels are essential whereby we conclude that spermine blocks the TRPC4 channel with electrostatic interaction between negative amino acids at the C-terminus of the channel.

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