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Am J Physiol Cell Physiol 293: C1645-C1659, 2007. First published September 13, 2007; doi:10.1152/ajpcell.00165.2007
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Voltage-gated Ca2+ currents are necessary for slow-wave propagation in the canine gastric antrum

Orline Bayguinov, Sean M. Ward, James L. Kenyon, and Kenton M. Sanders

Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada

Submitted 17 April 2007 ; accepted in final form 7 September 2007

Electrical slow waves determine the timing and force of peristaltic contractions in the stomach. Slow waves originate from a dominant pacemaker in the orad corpus and propagate actively around and down the stomach to the pylorus. The mechanism of slow-wave propagation is controversial. We tested whether Ca2+ entry via a voltage-dependent, dihydropyridine-resistant Ca2+ conductance is necessary for active propagation in canine gastric antral muscles. Muscle strips cut parallel to the circular muscle were studied with intracellular electrophysiological techniques using a partitioned-chamber apparatus. Slow-wave upstroke velocity and plateau amplitude decreased from the greater to the lesser curvature, and this corresponded to a decrease in the density of interstitial cells of Cajal in the lesser curvature. Slow-wave propagation velocity between electrodes impaling cells in two regions of muscle and slow-wave upstroke and plateau were measured in response to experimental conditions that reduce the driving force for Ca2+ entry or block voltage-dependent Ca2+ currents. Nicardipine (0.1–1 µM) did not affect slow-wave upstroke or propagation velocities. Upstroke velocity, amplitude, and propagation velocity were reduced in a concentration-dependent manner by Ni2+ (1–100 µM), mibefradil (10–30 µM), and reduced extracellular Ca2+ (0.5–1.5 mM). Depolarization (by 10–15 mM K+) or hyperpolarization (10 µM pinacidil) also reduced upstroke and propagation velocities. The higher concentrations (or lowest Ca2+) of these drugs and ionic conditions tested blocked slow-wave propagation. Treatment with cyclopiazonic acid to empty Ca2+ stores did not affect propagation. These experiments show that voltage-dependent Ca2+ entry is obligatory for the upstroke phase of slow waves and active propagation.

interstitial cells of Cajal; gastric motility; calcium channels; pacemaker activity



Address for reprint requests and other correspondence: K. M. Sanders, Dept. of Physiology and Cell Biology, Univ. of Nevada School of Medicine, Reno, NV 89557 (e-mail: kent{at}unr.edu)




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