Two Types of Cation Channel Activated by Stimulation of Muscarinic Receptors in Guinea-Pig Urinary Bladder Smooth Muscle
Journal of Pharmacological Sciences
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 voltageclamped 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
... rmeable tris + and glutamate − , respectively, demonstrated that the biphasic current is entirely composed of cation currents. Its initial peak phase was abolished by buffering intracellular Ca 2+ to a constant level of 100 nM or depleting intracellular Ca 2+ stores, and it was mimicked by the Ca 2+ releaser caffeine. Ca 2+ 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 [Ca 2+ ] i . These results demonstrate that muscarinic receptor stimulation invokes the openings of two types of cation channel, a Ca 2+ -activated and a receptor-operated type; the former channels are gated by a rise in [Ca 2+ ] i upon intracellular Ca 2+ release, and the latter are gated through other muscarinic receptor-coupled signal transduction mechanisms.