Modulation by L-type Ca2+ channels and apamin-sensitive K+ channels of muscarinic responses in cat chromaffin cells.
In the perfused cat adrenal gland stimulated with the muscarinic agonist methacholine chloride (100 microM for 3 min), two components were detected in the catecholamine secretory response: 1) an early phasic component that peaked at 300 ng/5 s catecholamine release and 2) a tonic component whose peak was transient and declined to a plateau of about 140 ng/5 s. Apamin (0.1 microM) increased the phasic component to 1,200 ng/5 s and the tonic component to approximately 350 ng/5 s. In single fura 2-loaded cat adrenal chromaffin cells, the cytosolic Ca2+ concentration ([Ca2+]i) also followed a biphasic pattern after stimulation with methacholine. Depletion of extracellular Ca2+ reduced the phasic [Ca2+]i peak by > 50% and the phasic secretory peak by approximately 90%; both the tonic components of [Ca2+]i and secretion were abolished. Depletion of intracellular Ca2+ pools decreased the phasic and tonic components of [Ca2+]i and secretion with respect to control values; however, the phasic components diminished more than the tonic components of [Ca2+]i and secretion. Although 3 microM furnidipine (a dihydropyridine L-type Ca2+ channel blocker) inhibited the phasic component of [Ca2+]i and secretion, its effects were more pronounced on the tonic component. omega-Conotoxin GVIA (1 microM, an N-type Ca2+ channel blocker) did not affect the [Ca2+]i or the methacholine secretory responses. The secretion peak seems to depend on both extracellular free Ca2+ (Cao2+) entry through L-type Ca2+ channels as well as on the mobilization of Ca2+ from intracellular stores; the plateau depends only on Cao2+ entry through L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Uceda
G
G
Departmento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Artalejo
A R
AR
de la Fuente
M T
MT
López
M G
MG
Albillos
A
A
Michelena
P
P
García
A G
AG
Montiel
C
C
D000313:Adrenal Medulla / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D002415:Cats; D004095:Dihydropyridines / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D007700:Kinetics; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D008978:Mollusk Venoms / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D004095:Dihydropyridines; D005456:Fluorescent Dyes; D008978:Mollusk Venoms; D010455:Peptides; D015221:Potassium Channels; D016210:Methacholine Chloride; C049925:fura-2-am; D001030:Apamin; D020866:omega-Conotoxin GVIA; C082391:furnidipine; D002118:Calcium; D016257:Fura-2