DOI QR코드

DOI QR Code

Modulation of Pacemaker Potentials by Pyungwi-San in Interstitial Cells of Cajal from Murine Small Intestine - Pyungwi-San and Interstitial Cells of Cajal -

  • Kim, Jung Nam (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Song, Ho Jun (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Lim, Bora (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Kwon, Young Kyu (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Kim, Byung Joo (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine)
  • 투고 : 2012.11.06
  • 심사 : 2012.11.28
  • 발행 : 2013.03.31

초록

Objective: Pyungwi-san (PWS) plays a role in a number of physiologic and pharmacologic functions in many organs. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We aimed to investigate the beneficial effects of PWS in mouse small-intestinal ICCs. Methods: Enzymatic digestion was used to dissociate ICCs from the small intestine of a mouse. The whole-cell patch-clamp configuration was used to record membrane potentials from the cultured ICCs. Results: ICCs generated pacemaker potentials in the GI tract. PWS produced membrane depolarization in the current clamp mode. Pretreatment with a $Ca^{2+}$-free solution and a thapsigargin, a $Ca^{2+}$-ATPase, inhibitor in the endoplasmic reticulum, eliminated the generation of pacemaker potentials. However, only when the thapsigargin was applied in a bath solution, the membrane depolarization was not produced by PWS. Furthermore, the membrane depolarizations due to PWS were inhibited not by U-73122, an active phospholipase C inhibitor, but by chelerythrine and calphostin C, protein kinase C inhibitors. Conclusions: These results suggest that PWS might affect GI motility by modulating the pacemaker activity in the ICCs.

키워드

참고문헌

  1. Heo J. [Dongeuibogam]. Seoul:Namsandang;1994. 435 p. Korean.
  2. Riedlinger JE, Tan PW, Lu W. Ping wei san, a Chinese medicine for gastrointestinal disorders. Ann Pharmacother. 2001;35(2):228-35. https://doi.org/10.1345/aph.10122
  3. Shin IS, Seo CS, Ha HK, Lee MY, Huang DS, Huh JI, et al. Genotoxicity assessment of Pyungwi-san (PWS), a traditional herbal prescription. J Ethnopharmacol. 2011;133(2):696-703. https://doi.org/10.1016/j.jep.2010.10.050
  4. Lee HS, Moon JY. [Scavenging property of Pyungwi-san herbal-acupuncture solution on ROS and RNS]. Korean J Oriental Physiology & Pathology. 2007;21(1):165-70. Korean.
  5. Ji HC, Baek TH. [A comparative study of Pyeongwi-san, Ijin-tang and Pyeongjintang extracts on indomethacininduced gastric mucosal lesions in mice.] J Korean Oriental Med. 2011;32(2):102-17. Korean.
  6. Shin IS, Kim JH, Ha HK, Huang DS, Huh JI, Shin HK. [Study on safety of Pyungwi-san in Sprague-Dawley rats]. Korean J Oriental Physiology & Pathology. 2010;24(3):426-9. Korean.
  7. Ward SM, Burns AJ, Torihashi S, Sanders KM. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol. 1994;480(Pt 1):91-7. https://doi.org/10.1113/jphysiol.1994.sp020343
  8. Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995;373(6512):347-9. https://doi.org/10.1038/373347a0
  9. Sanders KM. A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology. 1996;111(2):492-515. https://doi.org/10.1053/gast.1996.v111.pm8690216
  10. Koh SD, Jun JY, Kim TW, Sanders KM. A $Ca^{2+}$-inhibited non-selective cation conductance contributes to pacemaker currents in mouse interstitial cell of Cajal. J Physiol. 2002;540(Pt 3):803-14. https://doi.org/10.1113/jphysiol.2001.014639
  11. Kim BJ, Lim HH, Yang DK, Jun JY, Chang IY, Park CS, et al. Melastatin-type transient receptor potential channel 7 is required for intestinal pacemaking activity. Gastroenterology. 2005;129(5):1504-17. https://doi.org/10.1053/j.gastro.2005.08.016
  12. Huizinga JD, Zhu J, Molleman A. High-conductance chloride channels generate pacemaker currents in interstitial cells of Cajal. Gastroenterology. 2002;123(5):1627-36. https://doi.org/10.1053/gast.2002.36549
  13. Zhu MH, Kim TW, Ro S, Yan W, Ward SM, Koh SD, et al. A $Ca^{2+}$-activated Cl- conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity. J Physiol. 2009;587(Pt 20):4905-18. https://doi.org/10.1113/jphysiol.2009.176206
  14. Goto K, Matsuoka S, Noma A. Two types of spontaneous depolarizations in the interstitial cells freshly prepared from the murine small intestine. J Physiol. 2004;559(Pt 2):411-22. https://doi.org/10.1113/jphysiol.2004.063875
  15. Koh SD, Sanders KM, Ward SM. Spontaneous electrical rhythmicity in cultured interstitial cells of Cajal from the murine small intestine. J Physiol. 1998;513(Pt 1):203-13. https://doi.org/10.1111/j.1469-7793.1998.203by.x
  16. Ward SM, Ordog T, Koh SD, Baker SA, Jun JY, Amberg G, et al. Pacemaking in interstitial cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria. J Physiol. 2000;525 Pt 2:355-61. https://doi.org/10.1111/j.1469-7793.2000.t01-1-00355.x
  17. Choi S, Choi JJ, Jun JY, Koh JW, Kim SH, Kim DH, et al. Induction of pacemaker currents by DA-9701, a prokinetic agent, in interstitial cells of Cajal from murine small intestine. Mol Cells. 2009;27(3):307-12. https://doi.org/10.1007/s10059-009-0039-6
  18. Sakamoto T, Unno T, Matsuyama H, Uchiyama M, Hattori M, Nishimura M, et al. Characterization of muscarinic receptor-mediated cationic currents in longitudinal smooth muscle cells of mouse small intestine. J Pharmacol Sci. 2006;100(3):215-26. https://doi.org/10.1254/jphs.FP0050973
  19. Aiello EA, Clement-Chomienne O, Sontag DP, Walsh MP, Cole WC. Protein kinase C inhibits delayed rectifier K+ current in rabbit vascular smooth muscle cells. Am J Physiol. 1996;271(1 Pt 2):H109-19.
  20. Yamauchi Y, Ueda J, Ohsawa K. [A simultaneous determination of various main components in oriental pharmaceutical decoction"heii-san"by ion-pair highperformance liquid chromatography]. Yakugaku Zasshi. 1996;116(10):776-82. Japanese. https://doi.org/10.1248/yakushi1947.116.10_776