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Am J Physiol Gastrointest Liver Physiol 285: G1111-G1121, 2003. First published July 31, 2003; doi:10.1152/ajpgi.00152.2003
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NEUROREGULATION AND MOTILITY

Sodium current in human intestinal interstitial cells of Cajal

Peter R. Strege,1,2 Yijun Ou,1,2 Lei Sha,1,2 Adam Rich,1 Simon J. Gibbons,1,2 Joseph H. Szurszewski,1,2 Michael G. Sarr,3 and Gianrico Farrugia1,2

1Enteric Neuroscience Program, 2Division of Gastroenterology and Hepatology, and 3Department of Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905

Submitted 1 April 2003 ; accepted in final form 28 July 2003

Interstitial cells of Cajal (ICC) generate the electrical slow wave required for normal gastrointestinal motility. The ionic conductances expressed in human intestinal ICC are unknown. The aim of this study was to determine expression of a Na+ current in human intestinal ICC and to determine the effects of the Na+ current on the slow wave. Visually identified, freshly dissociated, single ICC were verified by the presence of c-kit mRNA by using single-cell RT-PCR. Standard whole cell currents were recorded from patch-clamped ICC held at -100 mV between pulse protocols. A Na+ current was identified in human intestinal ICC. The current activated at -55 mV and peaked at -30 mV. Extracellular N-methyl-D-glucamine abolished and QX-314 (500 µM) blocked the Na+ current, but nifedipine and Ni2+ did not. The Na+ current was activated by shear stress. Single-cell RT-PCR detected mRNA for the Na+ {alpha}-subunit SCN5A in single human intestinal ICC. Lidocaine (200 µm) and QX-314 (500 µM) decreased slow wave frequency, and stretch increased slow wave frequency. A mechanosensitive Na+ channel current is present in human intestinal ICC and appears to play a role in the control of intestinal motor function.

pacemaker; small intestine; patch clamp; smooth muscle



Address for reprint requests and other correspondence: G. Farrugia, Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, 200 First St. SW, Rochester, MN 55905 (E-mail: farrugia.gianrico{at}mayo.edu).




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