Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Calcitonin Gene-related Peptide Suppresses Pacemaker Currents by Nitric Oxide/cGMP-dependent Activation of ATP-sensitive K+ Channels in Cultured Interstitial Cells of Cajal from the Mouse Small Intestine

  • Choi, Seok (Department of Physiology, College of Medicine, Chosun University) ;
  • Parajuli, Shankar Prasad (Department of Physiology, College of Medicine, Chosun University) ;
  • Yeum, Cheol Ho (Department of Physiology, College of Medicine, Chosun University) ;
  • Park, Chan Guk (Department of Internal Medicine, College of Medicine, Chosun University) ;
  • Kim, Man Yoo (Department of Internal Medicine, College of Medicine, Chosun University) ;
  • Kim, Young Dae (Department of Internal Medicine, College of Medicine, Chosun University) ;
  • Cha, Kyoung Hun (Department of Pediatrics, College of Medicine, Chosun University) ;
  • Park, Young Bong (Department of Pediatrics, College of Medicine, Chosun University) ;
  • Park, Jong Seong (Department of Physiology Chonnam National University Medical School) ;
  • Jeong, Han Seong (Department of Physiology Chonnam National University Medical School) ;
  • Jun, Jae Yeoul (Department of Physiology, College of Medicine, Chosun University)
  • Received : 2008.01.23
  • Accepted : 2008.04.03
  • Published : 2008.08.31
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Abstract

The effects of calcitonin gene-related peptide (CGRP) on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine were investigated using the whole-cell patch clamp technique at $30^{\circ}C$. Under voltage clamping at a holding potential of -70 mV, CGRP decreased the amplitude and frequency of pacemaker currents and activated outward resting currents. These effects were blocked by intracellular $GDP{\beta}S$, a G-protein inhibitor and glibenclamide, a specific ATP-sensitive $K^+$ channels blocker. During current clamping, CGRP hyperpolarized the membrane and this effect was antagonized by glibenclamide. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor) or naproxen (a cyclooxygenase inhibitor) did not block the CGRP-induced effects, whereas pretreatment with ODQ (a guanylate cyclase inhibitor) or L-NAME (an inhibitor of nitric oxide synthase) did. In conclusion, CGRP inhibits pacemaker currents in ICC by generating nitric oxide via G-protein activation and so activating ATP-sensitive $K^+$ channels. Nitric oxide- and guanylate cyclase-dependent pathways are involved in these effects.

Keywords

Acknowledgement

Supported by : Chosun University

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