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Three Distinct Ca 2+ Influx Pathways Couple Acetylcholine Receptor Activation to Catecholamine Secretion from PC12 Cells
Author(s) -
Taylor Shafeena C.,
Peers Chris
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751583.x
Subject(s) - muscarine , acetylcholine , chemistry , methyllycaconitine , muscarinic acetylcholine receptor , extracellular , nicotinic agonist , exocytosis , acetylcholine receptor , muscarinic acetylcholine receptor m3 , receptor , cholinergic , secretion , medicine , biophysics , endocrinology , nicotinic acetylcholine receptor , biology , biochemistry
Abstract: Amperometry and microfluorimetry were employed to investigate the Ca 2+ ‐dependence of catecholamine release induced from PC12 cells by cholinergic agonists. Nicotine‐evoked exocytosis was entirely dependent on extracellular Ca 2+ but was only partly blocked by Cd 2+ , a nonselective blocker of voltagegated Ca 2+ channels. Secretion and rises of [Ca 2+ ] i observed in response to nicotine could be almost completely blocked by methyllycaconitine and α‐bungarotoxin, indicating that such release was mediated by receptors composed of α7 nicotinic acetylcholine receptor subunits. Secretion and [Ca 2+ ] i rises could also be fully blocked by co‐application of Cd 2+ and Zn 2+ . Release evoked by muscarine was also fully dependent on extracellular Ca 2+ . Muscarinic receptor activation stimulated release of Ca 2+ from a caffeine‐sensitive intracellular store, and release from this store induced capacitative Ca 2+ entry that could be blocked by La 3+ and Zn 2+ . This Ca 2+ entry pathway mediated all secretion evoked by muscarine. Thus, activation of acetylcholine receptors stimulated rises of [Ca 2+ ] i and exocytosis via Ca 2+ influx through voltage‐gated Ca 2+ channels, α7 subunit‐containing nicotinic acetylcholine receptors, and channels underlying capacitative Ca 2+ entry.