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

1. In smooth muscle of the guinea-pig bladder, either membrane potential re cordings 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 a ssociated contractions. These responses were abolished by alpha,beta-methyl ene ATP, suggesting that they resulted fr om the activation of purinoceptor s by neurally released ATP. 3. Nifedipine abolished action potentials leaving the underlying EJPs and r educed the amplitude of both nerve-evoked increases in [Ca2+](i) and associ ated contractions. The subsequent co-application of caffeine and ryanodine inhibited the residual responses without inhibiting EJPs. These results ind icate 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 co ntractions. These responses were abolished by hyoscine, indicating that the y resulted from the activation of muscarinic receptors by neurally released ACh. 5. Oscillatory increases in [Ca2+](i) and associated contractions were inhi bited by either nifedipine or caffeine, indicating that the stimulation of muscarinic receptors activates both Ca2+ influx through L-type Ca2+ channel s and Ca2+ release from intracellular Ca2+ stores.