TRPC4 Is an Essential Component of the Nonselective Cation Channel Activated by Muscarinic Stimulation in Mouse Visceral Smooth Muscle Cells

  • Lee, Kyu Pil (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Jun, Jae Yeoul (Department of Physiology, College of Medicine, Chosun University) ;
  • Chang, In-Youb (Department of Anatomy, College of Medicine, Chosun University) ;
  • Suh, Suk-Hyo (Department of Physiology, College of Medicine, Ewha Womans University) ;
  • So, Insuk (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Kim, Ki Whan (Department of Physiology and Biophysics, Seoul National University College of Medicine)
  • Received : 2005.08.30
  • Accepted : 2005.09.28
  • Published : 2005.12.31

Abstract

Classical transient receptor potential channels (TRPCs) are thought to be candidates for the nonselective cation channels (NSCCs) involved in pacemaker activity and its neuromodulation in murine stomach smooth muscle. We aimed to determine the role of TRPC4 in the formation of NSCCs and in the generation of slow waves. At a holding potential of -60 mV, $50{\mu}M$ carbachol (CCh) induced $I_{NSCC}$ of amplitude [$500.8{\pm}161.8pA$ (n = 8)] at -60 mV in mouse gastric smooth muscle cells. We investigated the effects of commercially available antibodies to TRPC4 on recombinant TRPC4 expressed in HEK cells and CCh-induced NSCCs in gastric smooth muscle cells. TRPC4 currents in HEK cells were reduced from $1525.6{\pm}414.4pA$ (n = 8) to $146.4{\pm}83.3pA$ (n = 10) by anti-TRPC4 antibody and $I_{NSCC}$ amplitudes were reduced from $230.9{\pm}36.3pA$ (n = 15) to $49.8{\pm}11.8pA$ (n = 9). Furthermore, $I_{NSCC}$ in the gastric smooth muscle cells of TRPC4 knockout mice was only $34.4{\pm}10.4pA$ (n = 8) at -60 mV. However, slow waves were still present in the knockout mice. Our data suggest that TRPC4 is an essential component of the NSCC activated by muscarinic stimulation in the murine stomach.

Keywords

Nonselective Cation Channel;Transient Receptor Potential Channel;TRPC4

Acknowledgement

Supported by : Ministry of Information and Communication, SNUH

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