Browse > Article

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)
Publication Information
Molecules and Cells / v.20, no.3, 2005 , pp. 435-441 More about this Journal
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;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 20  (Related Records In Web of Science)
연도 인용수 순위
1 Freichel, M., Suh, S. H., Pfeifer, A., Schweig, U., Trost, C., et al. (2001) Lack of an endothelial store-operated $Ca^{2+}$ current impairs agonist-dependent vasorelaxation in TRP4-/- mice. Nat. Cell Biol. 3, 121-127   DOI   ScienceOn
2 Komuro, T. and Zhou, D. S. (1996) Anti-c-kit protein immunoreactive cells corresponding to the interstitial cells of Cajal in the guinea-pig small intestine. J. Auton. Nerv. Syst. 61, 169-174   DOI   ScienceOn
3 Philipp, S., Hambrecht, J., Braslavski, L., Schroth, G., Freichel, M., et al. (1998) A novel capacitative calcium entry channel expressed in excitable cells. EMBO J. 17, 4274-4282   DOI   ScienceOn
4 Sanders, K. M. (1992) Ionic mechanisms of electrical rhythmicity in gastrointestinal smooth muscles. Annu. Rev. Physiol. 54, 439-453   DOI   ScienceOn
5 Suzuki, H., Takano, H., Yamamoto, Y., Komuro, T., Saito, M., et al. (2000) Properties of gastric smooth muscles obtained from mice which lack inositol triphosphate receptor. J. Physiol. 525, 105-111   DOI
6 Dickens, E. J., Hirst, G. D. S., and Tomita, T. (1999) Identification of rhythmically active cells in guinea-pig stomach. J. Physiol. 514, 515-531   DOI   ScienceOn
7 Huizinga, J. D., Thuneberg, L., Kluppel, M., Malysz, J., Mikkelsen, H. B., et al. (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373, 347-349   DOI   ScienceOn
8 Philipp, S., Trost, C., Warnat, J., Rautmann, J., Himmerkus, N., et al. (2000) TRP4 (CCE1) protein is part of native calcium release-activated $Ca^{2+}$-like channels in adrenal cells. J. Biol. Chem. 275, 23965-23972   DOI   ScienceOn
9 Schaefer, M., Plant, T. D., Stresow, N., Albrecht, N., and Schultz, G. (2002) Functional differences between TRPC4 splice variants. J. Biol. Chem. 277, 3752-3759   DOI   ScienceOn
10 Hirst, G. D. S., Bramich, N. J., Teramoto, N., Suzuki, H., and Edwards, F. R. (2002) Regenerative component of slow waves in the guinea-pig gastric antrum involves a delayed increase in $[Ca^{2+}]_i$ and $Cl^{-}$ channels. J. Physiol. 540, 907-919   DOI
11 Torihashi, S., Fujimoto, T., Trost, C., and Nakayama, S. (2002) Calcium oscillation linked to pacemaking of interstitial cells of Cajal. J. Biol. Chem. 277, 19191-19197   DOI   ScienceOn
12 Jung, S., Strotmann, R., Schultz, G., and Plant, T. D. (2002) TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells. Am. J. Physiol. Cell Physiol. 82, C347-359
13 Ward, S. M., Burns, A. J., Torihashi, S., and Sanders, K. M. (1994) Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J. Physiol. 480, 91-97
14 Zhu, M. H., Lee, Y. M., Jin, N. G., So, I., and Kim, K. W. (2003) The transient receptor potential protein homologue TRPC4/5 as a candidate for the nonselective cationic channel activated by muscarinic stimulation in the murine stomach. Neurophysiology 35, 302-307   DOI
15 Satoh, E., Ono, K., Xu, F., and Iijima, T. (2002) Cloning and functional expression of a novel splice variant of rat TRPC4. Circ. J. 66, 954-958   DOI   ScienceOn
16 Inoue, R., Okada, T., Onoue, H., Hara, Y., Shimizu, S., et al. (2001) The transient receptor potential protein homologue TRP6 is the essential component of vascular ${\alpha}1$-adrenoceptor-activated $Ca^{2+}$- permeable cation channel. Circ. Res. 88, 325-332   DOI   ScienceOn
17 Walker, R. L., Koh, S. D., Sergeant, G. P., Sanders, K. M., and Horowitz, B. (2002) TRPC4 current have properties similar to the pacemaker current in interstitial cells of Cajal. Am. J. Physiol. Cell Physiol. 283, 1637-1645   DOI
18 Koh, S. D., Jun, J. Y., Kim, T. W., and Sanders, K. M. (2002) A $Ca^{2+}$-inhibited non-selective cation conductance contributes to pacemaker currents in mouse interstitial cell of Cajal. J. Physiol. 540, 803-814   DOI   ScienceOn
19 Ishigawa, S., Komori, K., Nagao, T., and Suzuki, H. (1985) Effects of diltiazem on electrical responses evoked spontaneously or by electrical stimulation in the smooth muscle cells of the guinea-pig stomach. Br. J. Pharmacol. 86, 789-797   DOI   ScienceOn
20 Lee, Y. M., Kim, B. J., Kim, H. J., Yang, D. K., Zhu, M. H., et al. (2003) TRPC5 as a candidate for the nonselective cation channel activated by muscarinic stimulation in murine stomach. Am. J. Physiol. Gastrointest. Liver Physiol. 284, G604-G616
21 Walker, R. L., Hume, J. R., and Horowitz, B. (2001) Differential expression and alternative splicing of TRP channel genes in smooth muscles. Am. J. Physiol. 280, C1184-C1192
22 Schaefer, M., Plant, T. D., Obukhov, A. G., Hofmann, T., Gudermann, T., et al. (2000) Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. J. Biol. Chem. 275, 17517-17526   DOI   ScienceOn
23 Okada, T., Shimizu, S., Wakamori, M., Maeda, A., Kurosaki, T., et al. (1998) Molecular cloning and functional characterization of a novel receptor-activated TRP $Ca^{2+}$ channel from mouse brain. J. Biol. Chem. 273, 10279-10287   DOI   ScienceOn
24 Philipp, S., Cavalie, A., Freichel, M., Wissenbach, U., Zimmer, S., et al. (1996) A mammalian capacitative calcium entry channel homologous to Drosophila TRP and TRPL. EMBO J. 15, 6166-6171