Inhibition of Pacemaker Activity of Interstitial Cells of Cajal by Hydrogen Peroxide via Activating ATP-sensitive $K^+$ Channels

  • Choi Seok (Department of Physiology, College of Medicine, Chosun University) ;
  • Parajuli Shankar Prasad (Department of Physiology, College of Medicine, Chosun University) ;
  • Cheong Hyeon-Sook (Department of Genetic Engineering, College of Natural Science, Chosun University) ;
  • Paudyal Dilli Parasad (Department of Genetic Engineering, College of Natural Science, Chosun University) ;
  • Yeum Cheol-Ho (Department of Physiology, College of Medicine, Chosun University) ;
  • Yoon Pyung-Jin (Department of Physiology, College of Medicine, Chosun University) ;
  • Jun Jae-Yeoul (Department of Physiology, College of Medicine, Chosun University)
  • Published : 2007.02.28

Abstract

To investigate whether hydrogen peroxide($H_2O_2$) affects intestinal motility, pacemaker currents and membrane potential were recorded in cultured interstitial cells of Cajal(ICC) from murine small intestine by using a whole-cell patch clamp. In whole cell patch technique at $30^{\circ}C$, ICC generated spontaneous pacemaker potential under current clamp mode(I=0) and inward currents(pacemaker currents) under voltage clamp mode at a holding potential of -70 mV. When ICC were treated with $H_2O_2$ in ICC, $H_2O_2$ hyperpolarized the membrane potential under currents clamp mode and decreased both the frequency and amplitude of pacemaker currents and increased the resting currents in outward direction under voltage clamp mode. Also, $H_2O_2$ inhibited the pacemaker currents in a dose-dependent manner. Because the properties of $H_2O_2$ action on pacemaker currents were same as the effects of pinacidil(ATP-sensitive $K^+$ channels opener), we tested the effects of glibenclamide(ATP-sensitive $K^+$ channels blocker) on $H_2O_2$ action in ICC, and found that the effects of $H_2O_2$ on pacemaker currents were blocked by co- or pre- treatment of glibenclamide. These results suggest that $H_2O_2$ inhibits pacemaker currents of ICC by activating ATP-sensitive $K^+$ channels.

Keywords

References

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