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.
Yamamoto
Masayuki
M
Department of Pathogenic Veterinary Science, United Graduate School of Veterinary Science, Gifu University, Gifu, Japan.
Unno
Toshihiro
T
Matsuyama
Hayato
H
Kohda
Masanobu
M
Masuda
Noriyuki
N
Nishimura
Masakazu
M
Ishii
Toshiaki
T
Komori
Seiichi
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002412:Cations; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D002412:Cations; D007473:Ion Channels; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D002217:Carbachol; D012964:Sodium; D011188:Potassium; D002118:Calcium