Voltage-gated Ca2+ currents are necessary for slow-wave propagation in the canine gastric antrum.
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 Ca(2+) entry via a voltage-dependent, dihydropyridine-resistant Ca(2+) 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 Ca(2+) entry or block voltage-dependent Ca(2+) currents. Nicardipine (0.1-1 microM) did not affect slow-wave upstroke or propagation velocities. Upstroke velocity, amplitude, and propagation velocity were reduced in a concentration-dependent manner by Ni(2+) (1-100 microM), mibefradil (10-30 microM), and reduced extracellular Ca(2+) (0.5-1.5 mM). Depolarization (by 10-15 mM K(+)) or hyperpolarization (10 microM pinacidil) also reduced upstroke and propagation velocities. The higher concentrations (or lowest Ca(2+)) of these drugs and ionic conditions tested blocked slow-wave propagation. Treatment with cyclopiazonic acid to empty Ca(2+) stores did not affect propagation. These experiments show that voltage-dependent Ca(2+) entry is obligatory for the upstroke phase of slow waves and active propagation.
Bayguinov
Orline
O
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Ward
Sean M
SM
Kenyon
James L
JL
Sanders
Kenton M
KM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D020748:Mibefradil / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016065:Myoelectric Complex, Migrating / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D009532:Nickel / Q000378:metabolism; D010528:Peristalsis / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011706:Pyloric Antrum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D013997:Time Factors
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007211:Indoles; D015221:Potassium Channels; D020748:Mibefradil; C022838:nickel chloride; D020110:Pinacidil; D009532:Nickel; D009529:Nicardipine; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid