Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Carbachol Regulates Pacemaker Activities in Cultured Interstitial Cells of Cajal from the Mouse Small Intestine

  • So, Keum Young (Department of Anesthesiology, College of Medicine, Chosun University) ;
  • Kim, Sang Hun (Department of Anesthesiology, College of Medicine, Chosun University) ;
  • Sohn, Hong Moon (Department of Orthopedic Surgery, College of Medicine, Chosun University) ;
  • Choi, Soo Jin (Department of Radiology, College of Medicine, Gachon Universtiy) ;
  • Parajuli, Shankar Prasad (Department of Physiology, College of Medicine, Chosun Universtiy) ;
  • Choi, Seok (Department of Physiology, College of Medicine, Chosun Universtiy) ;
  • Yeum, Cheol Ho (Department of Physiology, College of Medicine, Chosun Universtiy) ;
  • Yoon, Pyung Jin (Department of Physiology, College of Medicine, Chosun Universtiy) ;
  • Jun, Jae Yeoul (Department of Physiology, College of Medicine, Chosun Universtiy)
  • Received : 2008.11.04
  • Accepted : 2009.03.24
  • Published : 2009.05.31
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Abstract

We studied the effect of carbachol on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine by muscarinic stimulation using a whole cell patch clamp technique and $Ca^{2+}$-imaging. ICC generated periodic pacemaker potentials in the current-clamp mode and generated spontaneous inward pacemaker currents at a holding potential of -70 mV. Exposure to carbachol depolarized the membrane and produced tonic inward pacemaker currents with a decrease in the frequency and amplitude of the pacemaker currents. The effects of carbachol were blocked by 1-dimethyl-4-diphenylacetoxypiperidinium, a muscarinic $M_3$ receptor antagonist, but not by methotramine, a muscarinic $M_2$ receptor antagonist. Intracellular $GDP-{\beta}-S$ suppressed the carbachol-induced effects. Carbachol-induced effects were blocked by external $Na^+$-free solution and by flufenamic acid, a non-selective cation channel blocker, and in the presence of thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum. However, carbachol still produced tonic inward pacemaker currents with the removal of external $Ca^{2+}$. In recording of intracellular $Ca^{2+}$ concentrations using fluo 3-AM dye, carbachol increased intracellular $Ca^{2+}$ concentrations with increasing of $Ca^{2+}$ oscillations. These results suggest that carbachol modulates the pacemaker activity of ICC through the activation of non-selective cation channels via muscarinic $M_3$ receptors by a G-protein dependent intracellular $Ca^{2+}$ release mechanism.

Keywords

Acknowledgement

Supported by : Chosun University

References

  1. Choi, S., Yeum, C.H., Chang, I.Y., You, H.J., Park, J.S., Jeong, H.S., So, I., Kim, K.W., and Jun, J.Y. (2006). Activating of ATPdependent $K^{+}$ channels comprised of $K_{ir}$ 6.2 and SUR 2B by $PGE_{2}$ through $EP_{2}$ receptor in cultured interstitial cells of Cajal from murine small intestine. Cell. Physiol. Biochem. 18, 187-198 https://doi.org/10.1159/000097516
  2. Epperson, A., Hatton, W.J., Callaghan, B., Doherty, P., Walker, R.L., Sanders, K.M., Ward, S.M., and Horowitz, B. (2000). Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal. Am. J. Physiol. Cell. Physiol. 279, C529-C539 https://doi.org/10.1152/ajpcell.2000.279.2.C529
  3. Hirst, G.D., and Edwards, F.R. (2004). Role of interstitial cells of Cajal in the control of gastric motility. J. Pharmacol. Sci. 96, 1-10 https://doi.org/10.1254/jphs.CRJ04002X
  4. Hirst, G.D., Dickens, E.J., and Edwards, F.R. (2002). Pacemaker shift in the gastric antrum of guinea-pigs produced by excitatory vagal stimulation involves intramuscular interstitial cells. J. Physiol. 541, 917-928 https://doi.org/10.1113/jphysiol.2002.018614
  5. Huizinga, J.D., Chang, G., Diamant, N.E., and El-Sharkawy, T.Y. (1984). Electrophysiological basis of excitation of canine colonic circular muscle by cholinergic agents and substance P. J. Pharmacol. Exp. Ther. 231, 692-699
  6. Inoue, R. (1991). Effect of external $Cd^{2+}$ and other divalent cations on carbachol-activated non-selective cation channels in guineapig ileum. J. Physiol. 442, 447-463 https://doi.org/10.1113/jphysiol.1991.sp018802
  7. Inoue, R., and Chen, S. (1993). Physiology of muscarinic receptoroperated nonselective cation channels in guinea-pig ileal smooth muscle. EXS. 66, 261-268
  8. Inoue, R., and Isenberg, G. (1990a). Intracellular calcium ions modulate acetylcholine-induced inward current in guinea-pig ileum. J. Physiol. 424, 73-92 https://doi.org/10.1113/jphysiol.1990.sp018056
  9. Inoue, R., and Isenberg, G. (1990b). Acetylcholine activates nonselective cation channels in guinea pig ileum through a G protein. Am. J. Physiol. 258, C1173-C1178 https://doi.org/10.1152/ajpcell.1990.258.6.C1173
  10. Jun, J.Y., Kong, I.D., Koh, S.D., Wang, X.Y., Perrino, B.A., Ward, S.M., and Sanders, K.M. (2001). Regulation of ATP-sensitive $K^{+}$ channels by protein kinase C in murine colonic myocytes. Am. J. Physiol. Cell. Physiol. 281, C857-C64 https://doi.org/10.1152/ajpcell.2001.281.3.C857
  11. Jun, J.Y., Choi, S., Yeum, C.H., Chang, I.Y., You, H.J., Park, C.K., Kim, M.Y., Kong, I.D., Kim, M.J., Lee, K.P., et al. (2004). Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine. Eur. J. Pharmacol. 495, 35-42 https://doi.org/10.1016/j.ejphar.2004.05.022
  12. Kim, T.W., Koh, S.D., Ordog, T., Ward, S.M., and Sanders, K.M. (2003). Muscarinic regulation of pacemaker frequency in murine gastric interstitial cells of Cajal. J. Physiol. 546, 415-425 https://doi.org/10.1113/jphysiol.2002.028977
  13. Kim, B.J., Lim, H.H., Yang, D.K., Jun, J.Y., Chang, I.Y., Park, C.S., So, I., Stanfield, P.R., and Kim, K.W. (2005). Melastatin-type transient receptor potential channel 7 is required for intestinal pacemaking activity. Gastroenterology 129, 1504-1517 https://doi.org/10.1053/j.gastro.2005.08.016
  14. Koh, S.D., Sanders, K.M., and Ward, S.M. (1998). Spontaneous electrical rhythmicity in cultured interstitial cells of cajal from the murine small intestine. J. Physiol. 513, 203-213 https://doi.org/10.1111/j.1469-7793.1998.203by.x
  15. 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 https://doi.org/10.1113/jphysiol.2001.014639
  16. Kuriyama, H., Kitamura, K., Itoh, T., and Inoue, R. (1998). Physiological features of visceral smooth muscle cells, with special reference to receptors and ion channels. Physiol. Rev. 78, 811-920 https://doi.org/10.1152/physrev.1998.78.3.811
  17. Nakayama, S., Ohya, S., Liu, H.N., Watanabe, T., Furuzono, S., Wang, J., Nishzawa, Y., Aoyama, M., Murase, N., Matsubara, T., et al. (2005). Sulphonylurea receptors differently modulate ICC pacemaker $Ca^{2+}$ activity and smooth muscle contractility. J. Cell. Sci. 118, 4163-4173 https://doi.org/10.1242/jcs.02540
  18. Olsson, C., and Holmgren, S. (2001). The control of gut motility. Comp. Biochem. Physiol. A. Mol. Integr. Physiol. 128, 481-503
  19. Sakamoto, T., Unno, T., Matsuyama, H., Uchiyama, M., Hattori, M., Nishimura, M., and Komori, S. (2006). Characterization of muscarinic receptor-mediated cationic currents in longitudinal smooth muscle cells of mouse small intestine. J. Pharmacol. Sci. 100, 215-226 https://doi.org/10.1254/jphs.FP0050973
  20. Sanders, K.M. (1998). G protein-coupled receptors in gastrointestinal physiology. IV. Neural regulation of gastrointestinal smooth muscle. Am. J. Physiol. 275, G1-G7 https://doi.org/10.1152/ajpcell.1998.275.3.Ca1
  21. Sanders, K.M., Koh, S.D., and Ward, S.M. (2006). Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu. Rev. Physiol.68, 307-343 https://doi.org/10.1146/annurev.physiol.68.040504.094718
  22. Sims, S.M. (1992). Cholinergic activation of a non-selective cation current in canine gastric smooth muscle is associated with contraction. J. Physiol. 449, 377-398 https://doi.org/10.1113/jphysiol.1992.sp019091
  23. Streutker, C.J., Huizinga, J.D., Driman, D.K., and Riddell, R.H. (2007). Interstitial cells of Cajal in health and disease. Part I: normal ICC structure and function with associated motility disorders. Histopathology. 50, 176-189 https://doi.org/10.1111/j.1365-2559.2006.02493.x
  24. Suzuki, H. (2000). Cellular mechanisms of myogenic activity in gastric smooth muscle. Jpn. J. Physiol. 50, 289-301 https://doi.org/10.2170/jjphysiol.50.289
  25. Szurszewski, J.H. (1987). Electrical basis for gastrointestinal motility. In Physiology of the Gastrointestinal Tract, L.R. Johnson, ed., 2nd ed. (New York, USA; Raven Press), pp. 383-422
  26. Thomsen, L., Robinson, T.L., Lee, J.C., Farraway, L.A., Hughes, M.J., Andrews, D.W., and Huizinga, J.D. (1998). Interstitial cells of Cajal generate a rhythmic pacemaker current. Nat. Med. 4, 848-851 https://doi.org/10.1038/nm0798-848
  27. Torihashi, S., Fujimoto, T., Trost, C., and Nakayama, S. (2002). Calcium oscillation linked to pacemaking of interstitial cells of Cajal: requirement of calcium influx and localization of TRP4 in caveolae. J. Biol. Chem. 277, 19191-19197 https://doi.org/10.1074/jbc.M201728200
  28. Unno, T., Matsuyama, H., Okamoto, H., Sakamoto, T., Yamamoto, M., Tanahashi, Y., Yan, H.D., and Komori, S. (2006). Muscarinic cationic current in gastrointestinal smooth muscles: signal transduction and role in contraction. Auton. Autacoid. Pharmacol. 26, 203-217 https://doi.org/10.1111/j.1474-8673.2006.00366.x
  29. Vogalis, F., and Sanders, K.M. (1990). Cholinergic stimulation activates a non-selective cation current in canine pyloric circular muscle cells. J. Physiol. 429, 223-236 https://doi.org/10.1113/jphysiol.1990.sp018253
  30. Walker, R.L., Koh, S.D., Sergeant, G.P., Sanders, K.M., and Horowitz, B. (2002). TRPC4 currents have properties similar to the pacemaker current in interstitial cells of Cajal. Am. J. Physiol. Cell. Physiol. 283, C1637-C1645 https://doi.org/10.1152/ajpcell.00266.2002
  31. Ward, S.M., and Sanders, K.M. (2006). Involvement of intramuscular interstitial cells of Cajal in neuroeffector transmission in the gastrointestinal tract. J. Physiol. 576, 675-682 https://doi.org/10.1113/jphysiol.2006.117390
  32. Ward, S.M., Ordog, T., Koh, S.D., Baker, S.A., Jun, J.Y., Amberg, G., Monaghan, K., and Sanders, K.M. (2002). Pacemaking in interstitial cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria. J. Physiol. 525, 355-361 https://doi.org/10.1111/j.1469-7793.2000.t01-1-00355.x
  33. Won, K.J., Sanders, K.M., and Ward, S.M. (2005). Interstitial cells of Cajal mediate mechanosensitive responses in the stomach. Proc. Natl. Acad. Sci. USA 102, 14913-14918 https://doi.org/10.1073/pnas.0503628102
  34. Zagorodnyuk, V., Santicioli, P., and Maggi, C.A. (1994). Different $Ca^{2+}$ influx pathways mediate tachykinin receptor-induced contraction in circular muscle of guinea-pig colon. Eur. J. Pharmacol. 255, 9-15 https://doi.org/10.1016/0014-2999(94)90076-0

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