Bayguinov Orline, Ward Sean M, Kenyon James L, Sanders Kenton M
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Am J Physiol Cell Physiol. 2007 Nov;293(5):C1645-59. doi: 10.1152/ajpcell.00165.2007. Epub 2007 Sep 13.
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.
电慢波决定胃蠕动收缩的时间和力量。慢波起源于胃体近端的一个主导起搏点，并围绕胃并向下主动传播至幽门。慢波传播的机制存在争议。我们测试了通过电压依赖性、二氢吡啶抗性钙电导的钙离子内流对于犬胃窦肌的主动传播是否必要。使用分隔腔装置，通过细胞内电生理技术研究了与环行肌平行切割的肌条。慢波上升速度和平台期振幅从大弯向小弯递减，这与小弯处 Cajal 间质细胞密度的降低相对应。在降低钙离子内流驱动力或阻断电压依赖性钙电流的实验条件下，测量了刺入肌肉两个区域细胞的电极之间的慢波传播速度以及慢波上升和平台期。尼卡地平（0.1 - 1 μM）不影响慢波上升或传播速度。镍离子（1 - 100 μM）、米贝拉地尔（10 - 30 μM）和降低细胞外钙离子浓度（0.5 - 1.5 mM）均以浓度依赖性方式降低慢波上升速度、振幅和传播速度。去极化（通过 10 - 15 mM 钾离子）或超极化（10 μM 吡那地尔）也降低慢波上升和传播速度。所测试的这些药物的较高浓度（或最低钙离子浓度）以及离子条件阻断了慢波传播。用环匹阿尼酸处理排空钙离子储存并不影响传播。这些实验表明，电压依赖性钙离子内流对于慢波的上升期和主动传播是必需的。
