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)