Two Types of Cation Channel Activated by Stimulation of Muscarinic Receptors in Guinea-Pig Urinary Bladder Smooth Muscle

The present study, aiming to elucidate ion channel mechanisms underlying muscarinic receptor-induced depolarization, has characterized membrane currents induced by carbachol in single guinea-pig urinary bladder myocytes. Application of carbachol to cells that were voltage-clamped at -50 mV produced an atropine-sensitive, biphasic inward current consisting of an initial peak followed by a smaller sustained phase. Replacing the extracellular Na+ and intracellular Cl- with impermeable tris(+) and glutamate(-), respectively, demonstrated that the biphasic current is entirely composed of cation currents. Its initial peak phase was abolished by buffering intracellular Ca2+ to a constant level of 100 nM or depleting intracellular Ca2+ stores, and it was mimicked by the Ca2+ releaser caffeine. Ca2+ entry evoked by voltage steps in the sustained phase induced no noticeable change, indicating that this phase of cation current is insensitive to a rise of [Ca2+](i). These results demonstrate that muscarinic receptor stimulation invokes the openings of two types of cation channel, a Ca2+-activated and a receptor-operated type; the former channels are gated by a rise in [Ca2+](i) upon intracellular Ca2+ release, and the latter are gated through other muscarinic receptor-coupled signal transduction mechanisms.