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 [Ca 2+]i upon intracellular Ca2+ release, and the latter are gated through other muscarinic receptor-coupled signal transduction mechanisms. ©2008 The Japanese Pharmacological Society.
CITATION STYLE
Yamamoto, M., Unno, T., Matsuyama, H., Kohda, M., Masuda, N., Nishimura, M., … Komori, S. (2008). Two types of cation channel activated by stimulation of muscarinic receptors in guinea-pig urinary bladder smooth muscle. Journal of Pharmacological Sciences, 108(3), 248–257. https://doi.org/10.1254/jphs.08138FP
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