Korean J Gastroenterol.  2003 Aug;42(2):121-127.

Characterization of Pacemaking Currents in Cultured Interstitial Cells of Cajal from Mice Small Intestine

• Chang SJ
• Cho ET
• Heo GS
• Park CG
• Kim MW
• Chang IY
• Shin MK
• Cha KH
• Yeum CH
• Jun JY

Abstract

BACKGROUND/AIMS: Gastrointestinal motility is initiated by the periodic generation of slow waves. Interstitial cells of Cajal (ICC) are pacemaker cells that generate slow waves and drive spontaneous mechanical contractions of the gastrointestinal smooth muscle. Slow waves generate the periodic activation of spontaneous inward currents (pacemaker currents). The aim of this study was to investigate the characterization of pacemaker currents of ICC. METHODS: The ICC in mice small intestine were cultured with stem cell factor for 2 days, and then we recorded pacemaker currents and slow waves using a whole-cell patch clamp technique. RESULTS: Under voltage clamp at -80 mV of holding potential, ICC generated pacemaker currents. Tetrodotoxin and nifedipine did not affect on the pacemaker currents. In addition, tetraethylammonium, 4-aminopyridine and glibenclamide did not affect on the pacemaker currents. The reduction of external Na+ concentrations inhibited pacemaker currents. Moreover, these currents were completely abolished in the external Ca2+-free condition. Gadolinium and flufenamic acid, inhibitors of non-selective cationic currents, inhibited pacemaker currents. Thapsigargin and cyclopiazoic acid, inhibitors of Ca2+-ATPase in endoplasmic reticulum, abolished pacemaker currents. Carbachol depolarized membrane potential and increased inward currents. CONCLUSIONS: These results suggest that pacemaker currents are mediated by the activation of non-selective cation channel and become a target of neurotransmitters in regulation of intestinal motility.

Keyword

Interstitial cells of Cajal; Pacemaker currents; Non-selective cation channel; Carbachol; Gastrointestinal motility

MeSH Terms

Animals
Cells, Cultured
Electrophysiology
Gastrointestinal Motility/*physiology
Intestine, Small/*cytology
Ion Channels/drug effects
Membrane Potentials/drug effects
Mice
Mice, Inbred BALB C
Muscle, Smooth/cytology/physiology
Patch-Clamp Techniques