Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder.

1. In smooth muscle of the guinea-pig bladder, either membrane potential recordings or [Ca2+]i measurements were made simultaneously with isometric tension recordings. 2. Single transmural stimuli initiated excitatory junction potentials (EJPs) which triggered action potentials, transient increases in [Ca2+]i and associated contractions. These responses were abolished by alpha, beta-methylene ATP, suggesting that they resulted from the activation of purinoceptors by neurally released ATP. 3. Nifedipine abolished action potentials leaving the underlying EJPs and reduced the amplitude of both nerve-evoked increases in [Ca2+]i and associated contractions. The subsequent co-application of caffeine and ryanodine inhibited the residual responses without inhibiting EJPs. These results indicate that stimulation of purinoceptors activates both Ca2+ influx through L-type Ca2+ channels and Ca2+ release from intracellular Ca2+ stores. 4. In the presence of alpha, beta-methylene ATP, trains of stimuli failed to initiate EJPs but increased the frequency of action potentials. Trains of stimuli also initiated oscillatory increases in [Ca2+]i and associated contractions. These responses were abolished by hyoscine, indicating that they resulted from the activation of muscarinic receptors by neurally released ACh. 5. Oscillatory increases in [Ca2+]i and associated contractions were inhibited by either nifedipine or caffeine, indicating that the stimulation of muscarinic receptors activates both Ca2+ influx through L-type Ca2+ channels and Ca2+ release from intracellular Ca2+ stores.