CONSEQUENCES OF METABOLIC INHIBITION IN SMOOTH-MUSCLE ISOLATED FROM GUINEA-PIG STOMACH

1. In smooth muscle isolated from the guinea-pig stomach, cyanide (CN) and iodoacetic acid (IAA) were applied to block oxidative phosphoryla tion and glycolysis, respectively. Effects of IAA on generation of spo ntaneous mechanical and electrical activities were systematically inve stigated by comparing those of CN. Spontaneous activity ceased in 10-2 0 min during applications of 1 mM IAA. On the other hand, application of 1 mM CN also reduced the spontaneous activity, but never terminated it. In the presence of CN the negativity of the resting membrane pote ntial was slightly reduced. 2. When spontaneous activity ceased with I AA, the resting membrane potential was not significantly affected. Als o, before ceasing, the amplitude and duration of the spontaneous elect rical activity were significantly reduced. The amplitude of the electr otonic potential was, however, not changed by IAA. Further, glibenclam ide did not prevent the effects of IAA. These results suggest that, un like cardiac muscle, activation of metabolism-dependent K+ channels in stomach smooth muscle does not seem to play a major role in reducing and terminating spontaneous activity during metabolic inhibition. 3. C arbachol-induced contraction transiently increased, and subsequently d ecreased gradually during application of IAA. 4. After 50 min applicat ion of IAA, when there was no spontaneous activity, the concentrations of phosphocreatine (PCr) and ATP measured with P-31 nuclear magnetic resonance decreased to 60 and 80% of the control, respectively, while inorganic phosphate (P-i) concentration paradoxically fell to below de tectable levels. During subsequent prolonged application of IAA, high- energy phosphates steadily decreased. On the other hand, after 50 min CN application, [PCr] and [ATP] decreased to approximately 30 and 80% of the control, respectively, while [P-i] increased by 2.6-fold. 5. In the presence of either CN or IAA, spontaneous mechanical and electric al activities were reduced or eliminated, although amounts of high-ene rgy phosphates sufficient to contract smooth muscle remained. It can b e postulated that some mechanism(s) related to energy metabolism, but not including ATP-sensitive K+ channels, plays an important role in ge nerating spontaneous activity in guinea-pig stomach smooth muscle. Dur ing metabolic inhibition the energy metabolism-dependent mechanism(s) would preserve high-energy phosphates, and consequently cell viability by stopping spontaneous activity.