Muscarinic receptor agonist-induced increases in cytosolic Ca2+ concentrations in chick ciliary ganglion cells.
We used fura-2 microfluorometry to examine the mechanism underlying the muscarinic receptor agonist-induced increase in the cytosolic Ca2+ concentration ([Ca]in) in acutely isolated chick ciliary ganglion neurons. The order of potencies of muscarinic agonists in increasing [Ca]in was: oxotremorine M > muscarine > methacholine > oxotremorine > bethanechol. The muscarine-induced increase in [Ca]in persisted after treatment with thapsigargin, which blocked caffeine- and muscarinic agonist-induced Ca2+ release. The muscarine-sensitive [Ca]in increase was inhibited by both L- and N-type Ca2+ channel blockers but potentiated by an L-type Ca2+ channel agonist. Muscarine was effective in increasing [Ca]in in the presence of a desensitizing concentration of nicotine, and simultaneous addition of maximal doses of muscarine and nicotine caused an additive increase in [Ca]in. On the other hand, nicotine-, ATP-, and high K(+)-induced increase in [Ca]in was markedly potentiated during continuous stimulation with muscarine. These results suggest that muscarinic receptor stimulation increases Ca2+ influx passing through voltage-dependent Ca2+ channels. However, the muscarine-induced Mn2+ influx was observed in only some muscarine-sensitive cells, suggesting that muscarine-induced depolarization is too weak to overcome the inhibitory effect of Mn2+ on Ca2+ channels.
Sorimachi
M
M
Department of Physiology, Kagoshima University School of Medicine, Japan.
Furukawa
K
K
Abe
Y
Y
Akaike
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002642:Chick Embryo; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D016257:Fura-2; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D008345:Manganese; D012964:Sodium; D011188:Potassium; D002118:Calcium; D016257:Fura-2