ROLE OF EXTRACELLULAR AND INTRACELLULAR CALCIUM IN THE CONTRACTILE ACTION OF AGONISTS IN THE GUINEA-PIG ILEUM

The effects of Ca2+ -channel blockers (nifedipine and verapamil), EGTA, caffeine or the removal of external Ca2+ on the contractile action of different agonists and transmural electrical stimulation were examined in isolated segments of the proximal and terminal part of the guinea-pig ileum. The effects of agonists and nerve stimulation on membrane potential were also studied by means of the sucrose gap method. Acetylcholine-elicited contractions in both parts and noradrenaline- as well as histamine-induced contractions in the terminal part of the ileum were composed of an initial phasic and a sustained tonic component. Single pulse transmural nerve stimulation elicited smooth muscle twitches, whereas addition of CaCl2 to the tissue bath containing Ca2+ -free and high-K+ medium elicited a sustained contraction. Both verapamil and nifedipine were more potent in inhibiting the tonic phase of the responses to the agonists or CaCl2 than inhibiting the phasic contractions elicited by transmural nerve stimulation, acetylcholine or noradrenaline. The excitatory junction potentials (e.j.p.s.) as well as smooth muscle twitches were reduced only by high nifedipine concentrations. The effects of acetylcholine on membrane potential and input membrane resistance were affected minimally by the omission of extracellular Ca2+, while the contractions gradually disappeared on repetitive agonist application in the absence of external Ca2+ and were blocked by caffeine preexposure. In Ca2+ -free solution noradrenaline and histamine partially reduced each other's motor effect, while neither of them changed the contractile action of acetylcholine, yet the contraction induced by noradrenaline was prevented and that of histamine significantly reduced by preexposure to acetylcholine. These results suggest that the potency of acetylcholine to release Ca2+ from its caffeine-sensitive intracellular stores is much higher than that of histamine and noradrenaline.