Electrical activity induced by nitric oxide in canine colonic circular muscle

Abstract

Nitric oxide generates slow electrical oscillations (SEOs) in cells near the myenteric edge of the circular muscle layer, which resemble slow waves generated by interstitial cells of Cajal (ICCs) at the submucosal edge of this muscle. The properties of SEOs were studied to determine whether these events are similar to slow waves. Rapid frequency membrane potential oscillations (MPOs; 16 ± 1 cycles/min and 9.6 ± 0.2 mV) were recorded from control muscles near the myenteric edge. Sodium nitroprusside (0.3 μM) reduced MPOs and initiated SEOs (1.3 ± 0.3 cycles/min and 13.4 ± 1.4 mV amplitude). SEOs were abolished by the guanylate cyclase inhibitor 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxaline-1-one (10 μM). MPOs were abolished by nifedipine (1 μM), whereas SEO frequency increased and the amount of depolarization decreased. BAY K 8644 (1 μM) prolonged SEOs and reduced their frequency. SEOs were abolished by Ni2+ (0.5 mM), low Ca2+ solution (0.1 mM Ca2+), cyclopiazonic acid (10 μM), and the mitochondrial uncouplers antimycin (10 μM) and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (1 μM). Oligomycin (10 μM) was without effect. These effects are similar to those described for colonic slow waves. Our results suggest that nitric oxide-induced SEOs are similar in mechanism to slow waves, an activity not previously thought to be generated by myenteric pacemakers.