Involvement of mitochondrial Na+-Ca2+ exchange in intestinal pacemaking activity.
OBJECTIVE
Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We have aimed to investigate the involvement of mitochondrial Na+-Ca2+ exchange in intestinal pacemaking activity in cultured interstitial cells of Cajal.


METHODS
Enzymatic digestions were used to dissociate ICCs from the small intestine of a mouse. The whole-cell patch-clamp configuration was used to record membrane currents (voltage clamp) and potentials (current clamp) from cultured ICCs.


RESULTS
Clonazepam and CGP37157 inhibited the pacemaking activity of ICCs in a dose-dependent manner. Clonazepam from 20 to 60 micromol/L and CGP37157 from 10 to 30 micromol/L effectively inhibited Ca2+ efflux from mitochondria in pacemaking activity of ICCs. The IC50s of clonazepam and CGP37157 were 37.1 and 18.2 micromol/L, respectively. The addition of 20 micromol/L NiCl2 to the internal solution caused a "wax and wane" phenomenon of pacemaking activity of ICCs.


CONCLUSIONS
These results suggest that mitochondrial Na+-Ca2+ exchange has an important role in intestinal pacemaking activity.
Kim
Byung Joo
BJ
Department of Physiology and Biophysics, College of Medicine, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea.
Jun
Jae Yeoul
JY
So
Insuk
I
Kim
Ki Whan
KW
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013841:Thiazepines / Q000494:pharmacology
D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D002998:Clonazepam; C079032:CGP 37157; D009532:Nickel