Effects of excitatory neurotransmitters on Ca2+ channel current in smooth muscle cells isolated from guinea‐pig urinary bladder

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Abstract
A whole‐cell voltage clamp technique was used to examine the effects of purinoceptor and muscarinic receptor agonists on voltage‐sensitive Ca2+ channels in guinea‐pig isolated urinary bladder cells. When the cell membrane was clamped at the holding potential, rapid application of ATP elicited a large inward current in normal solution containing 2.5 mm Ca2+, and reduced the subsequent Ca2+ channel current evoked by a depolarizing pulse (0 mV). Carbachol (CCh) elicited little membrane current, but similarly reduced the Ca2+ current. When purinoceptor agonists were rapidly applied during conditioning depolarizations at +80 mV, an outward current was elicited, and the Ca2+ channel current evoked by the subsequent test potential of 0 mV was not affected. Application of CCh at +80 mV also elicited an outward current, but it reduced the subsequently evoked Ca2+ current. The inhibitory effect of muscarinic agonists on the Ca2+ channel current was attenuated by caffeine (10 mm). In Ca2+‐free, low‐Mg2+ solution, a Na+ current flowing through voltage‐dependent Ca2+ channels was evoked by depolarization. This current was not reduced by bath application of purinoceptor agonists (ATP and α,β‐methylene ATP). These results suggest that the main effect of purinoceptor stimulation is opening of non‐selective cation channels, and that muscarinic stimulation triggers Ca2+ release from intracellular stores. Voltage‐sensitive Ca2+ channels are inactivated through an increase in intracellular Ca2+ induced by either activation of purinoceptor or muscarinic receptors.