Acetylcholine induces voltage-independent increase of cytosolic calcium in mouse myotubes.
Electrophysiological, biochemical, and Ca2+ imaging studies of cultured mouse myotubes were used to investigate whether the neurotransmitter acetylcholine causes an increase in intracellular Ca2+ concentration ([Ca2+]i) through activation of a second messenger system. Bath applications of acetylcholine to myotubes (i) elicited a significant membrane current even in a Na(+)-free Ca2+ medium, when the current was carried mainly by calcium ions; (ii) caused a rapid and transient cytosolic accumulation of inositol 1,4,5-trisphosphate; (iii) evoked a conspicuous alpha-bungarotoxin-sensitive long-lasting [Ca2+]i enhancement even in the presence of Cd2+; and (iv) transiently increased [Ca2+]i when cells were equilibrated in a Ca(2+)-free atropine-containing medium. We propose that, in addition to opening ion channels, the nicotinic action of acetylcholine on the muscle cell membrane increases [Ca2+]i through activation of the inositol 1,4,5-trisphosphate second messenger system and mobilization of Ca2+ from intracellular stores.
Giovannelli
A
A
Laboratorio di Biofisica, Centro della Ricerca Sperimentale Istituto Regina Elena, Rome, Italy.
Grassi
F
F
Mattei
E
E
Mileo
A M
AM
Eusebi
F
F
Giovanelli
A
A
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002412:Cations; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D016257:Fura-2; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009132:Muscles / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology; D012265:Ribonucleotides / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence
D002412:Cations; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011950:Receptors, Cholinergic; D012265:Ribonucleotides; D015544:Inositol 1,4,5-Trisphosphate; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D016257:Fura-2