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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS
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
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