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Am J Physiol Gastrointest Liver Physiol 292: G734-G745, 2007. First published November 22, 2006; doi:10.1152/ajpgi.00428.2006
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NEUROREGULATION AND MOTILITY

Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine?

E. E. Daniel, Ahmed El Yazbi, Marco Mannarino, Gary Galante, Geoffrey Boddy, Jonathan Livergant, and Tahereh Eteraf Oskouei

Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada

Submitted 15 September 2006 ; accepted in final form 11 November 2006

Varicosities of nitrergic and other nerves end on deep muscular plexus interstitial cells of Cajal or on CD34-positive, c-kit-negative fibroblast-like cells. Both cell types connect to outer circular muscle by gap junctions, which may transmit nerve messages to muscle. We tested the hypotheses that gap junctions transmit pacing messages from interstitial cells of Cajal of the myenteric plexus. Effects of inhibitors of gap junction conductance were studied on paced contractions and nerve transmissions in small segments of circular muscle of mouse intestine. Using electrical field stimulation parameters (50 V/cm, 5 pps, and 0.5 ms) which evoke near maximal responses to nitrergic, cholinergic, and apamin-sensitive nerve stimulation, we isolated inhibitory responses to nitrergic nerves, inhibitory responses to apamin-sensitive nerves and excitatory responses to cholinergic nerves. 18beta-Glycyrrhetinic acid (10, 30, and 100 µM), octanol (0.1, 0.3, and 1 mM) and gap peptides (300 µM of 40Gap27, 43Gap26, 37,43Gap27) all failed to abolish neurotransmission. 18beta-Glycyrrhetinic acid inhibited frequencies of paced contractions, likely owing to inhibition of L-type Ca2+ channels in smooth muscle, but octanol or gap peptides did not. 18beta-Glycyrrhetinic acid and octanol, but not gap peptides, reduced the amplitudes of spontaneous and nerve-induced contractions. These reductions paralleled reductions in contractions to exogenous carbachol. Additional experiments with gap peptides in both longitudinal and circular muscle segments after NG-nitro-L-arginine and TTX revealed no effects on pacing frequencies. We conclude that gap junction coupling may not be necessary for pacing or nerve transmission to the circular muscle of the mouse intestine.

nitric oxide; adenosine 5'-triphosphate; inhibitory nerve transmission; cholinergic nerve transmission; interstitial cells of Cajal; pacing of intestinal muscle



Address for reprint requests and other correspondence: E. E. Daniel, Rm. 9-10, Medical Sciences Bldg., Dept. of Pharmacology, Faculty of Medicine and Dentistry, Univ. of Alberta, Edmonton, Alberta, Canada T6G 2H7 (e-mail: edaniel{at}ualberta.ca)







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