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World J Gastroenterol. Feb 7, 2006; 12(5): 796-799
Published online Feb 7, 2006. doi: 10.3748/wjg.v12.i5.796
Involvement of mitochondrial Na+–Ca2+ exchange in intestinal pacemaking activity
Byung Joo Kim, Jae Yeoul Jun, Insuk So, Ki Whan Kim
Byung Joo Kim, Insuk So, Ki Whan Kim, Department of Physiology and Biophysics, College of Medicine, Seoul National University, Republic of Korea
Jae Yeoul Jun, Department of Physiology, College of Medicine, Chosun University, Republic of Korea
Supported by the Seoul National University Hospital Research Fund (03-2004-008), Korea Research Foundation Grant funded by Korea Government (MOEHRD, Basic Research Promotion Fund, KRF-2004-041-E00022) and BK21 project for medicine, dentistry, and pharmacy
Correspondence to: Insuk So, MD, PhD, Department of Physiology and Biophysics, College of Medicine, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea. insuk@plaza.snu.ac.kr
Telephone: +82-2-740-8228 Fax: +82-2-763-9667
Received: July 13, 2005
Revised: August 9, 2005
Accepted: August 31, 2005
Published online: February 7, 2006
Abstract

AIM: 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 µmol/L and CGP37157 from 10 to 30 µmol/L effectively inhibited Ca2+ efflux from mitochondria in pacemaking activity of ICCs. The IC50s of clonazepam and CGP37157 were 37.1 and 18.2 µmol/L, respectively. The addition of 20 µmol/L NiCl2 to the internal solution caused a “wax and wane” phenomenon of pacemaking activity of ICCs.

CONCLUSION: These results suggest that mitochondrial Na+-Ca2+ exchange has an important role in intestinal pacemaking activity.

Keywords: Mitochondrial Na+-Ca2+ exchange, Interstitial cells of Cajal