Large- and small-conductance Ca(2+)-activated K+ channels: their role in the nicotinic receptor-mediated catecholamine secretion in bovine adrenal medulla.
In cultured bovine adrenal chromaffin cells, charybdotoxin and iberiotoxin (inhibitors of the large-conductance Ca(2+)-activated K+ channel) as well as apamin (an inhibitor of the small-conductance Ca(2+)-activated K+ channel), at 1-100 nM, suppressed carbachol-induced 86RB+ efflux, augmented carbachol-induced 45Ca2+ influx via voltage-dependent Ca2+ channels and catecholamine secretion and had no effect on carbachol-induced 22Na+ influx via nicotinic receptors, a prerequisite for Ca2+ channel activation by carbachol. 45Ca2+ influx caused by high K+ (a direct activation of voltage-dependent Ca2+ channels) was also enhanced by these K+ channel inhibitors, with the concentration-response curves being similar to those for carbachol-induced 45Ca2+ influx. Dendrotoxin and mast cell degranulating peptide (inhibitors of voltage-dependent K+ channels), on the other hand, did not alter carbachol-induced 86Rb+ efflux or 45Ca2+ influx. These results suggest that the stimulation of nicotinic receptors eventually opens large- and small-conductance Ca(2+)-activated K+ channels, and that the blockade of these Ca(2+)-activated K+ channels results in gating of voltage-dependent Ca2+ channels and thereby augments catecholamine secretion from bovine adrenal chromaffin cells.
Wada
A
A
Department of Pharmacology, Miyazaki Medical College, Japan.
Urabe
M
M
Yuhi
T
T
Yamamoto
R
R
Yanagita
T
T
Niina
H
H
Kobayashi
H
H
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D017136:Ion Transport; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D012413:Rubidium / Q000378:metabolism
D002395:Catecholamines; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011978:Receptors, Nicotinic; D018999:Charybdotoxin; D001030:Apamin; C064719:iberiotoxin; D002217:Carbachol; D012413:Rubidium; D002118:Calcium