Effects of hypoxia on stimulus-release coupling mechanisms in cultured bovine adrenal chromaffin cells.
To clarify the effects of hypoxia on stimulus-release coupling, we have examined the effects of hypoxia on nicotine-induced catecholamine (noradrenaline and adrenaline) release from, and 22Na+ influx, 45Ca2+ influx and cytosolic free Ca2+ concentration ([Ca2+]i) in, cultured bovine adrenal chromaffin cells. Experiments were carried out in media pre-equilibrated with 21% O2/79% N2 (control) or with 0% O2/100% N2 (hypoxia). Cells were stimulated with either nicotine (activating nicotinic acetylcholine (ACh) receptors) or a high K+ concentration (55 mmol/l KCl; directly activating voltage-dependent Ca2+ channels). Hypoxia reduced both nicotine- and high K(+)-induced catecholamine releases from the cells, but the reduction of the former (to about 30% of the control value) was more pronounced than that of the latter (to about 40% of the control value). Nicotine-induced 22Na+ influx, which is considered to reflect the function of nicotinic ACh receptors, was inhibited by hypoxia. Both nicotine- and high K(+)-induced 45Ca2+ influx into the cells were reduced by hypoxia, but the reduction of the former was more pronounced than that of the latter. Nicotine- and high K(+)-induced increases in [Ca2+]i were reduced by hypoxia to about 30% and 40% of the control values, respectively. These results suggest that hypoxia reduces cation influxes (Na+ and Ca2+) through both the ligand-gated cation channels of the nicotinic ACh receptor and the voltage-dependent Ca2+ channels.
Lee
K
K
Department of Physiology, Gifu University School of Medicine, Japan.
Sekine
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004759:Enterochromaffin Cells / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D012979:Sodium Radioisotopes
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D002395:Catecholamines; D011950:Receptors, Cholinergic; D012979:Sodium Radioisotopes; D009538:Nicotine; D012964:Sodium; D011188:Potassium; D002118:Calcium