Modulation by L-type Ca2+ channels and apamin-sensitive K+ channels of muscarinic responses in cat chromaffin cells

Abstract

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)

Ca2+‐Dependent K+ Currents Induced by Muscarinic Receptor Activation in Guinea Pig Adrenal Chromaffin Cells

“…Therefore, the activation of K~channels by elevated~Ca2~]would counteract the actions elicited by membrane depolarization and lead to a limit of further excitation (Tse and Hille, 1992). In fact, Ca2t dependent K~channel blockers have been reported to potentiate secretory responses to transmural electrical stimulation (Montiel et al, 1995) and to muscarinic stimulation (Uceda et al, 1992(Uceda et al, , 1994 in perfused cat adrenal glands. To define the physiological significance of Ca2tdependent K~channels in detail, further experiments must be performed, measuring simultaneously the secretory and current responses at a singlecell level.…”

Calcium Signaling and Exocytosis in Adrenal Chromaffin Cells

“…However, the various calcium channel subtypes suffer different degrees of inactivation, depending on the [Ca 2ϩ ] c (193) and on the membrane potential (390). Furthermore, chromaffin cells express small-conductance Ca 2ϩ -dependent K ϩ channels (24) that will also contribute to the regulation of action potential firing and exocytosis (271,381). In summary, all these observations suggest that each type of calcium channel could exhibit different efficacies in triggering and controlling the secretory process, and the experimental conditions must be appropriately selected to reveal these differences.…”

Large- and small-conductance Ca2+-activated K+ channels: their role in the nicotinic receptor-mediated catecholamine secretion in bovine adrenal medulla

“…In cells loaded with 86Rb+, carbachol-induced influx of Na + and Ca 2+ stimulates the efflux of 86Rb+ (Wada et al 1987), in accordance with patch clamp studies (Marty 1981;Marty and Neher 1985;Artalejo et al 1993) showing that depolarization-induced Ca 2+ influx via Ca 2+ channels increases both the small-conductance (IsK(ca)) and the large-conductance (IB~c(ca)) Ca2+-dependent K + currents. Although, in the cat adrenal medulla, blockers of SK channels augmented the muscarinic agonist-induced catecholamine secretion and rise in [Ca2+]i as a consequence of L-type Ca 2+ channel activation (Uceda et al 1992(Uceda et al , 1994, the role of BK channels and the modulation of K + channel activity by the channel inhibitors have not been examined in relation to catecholamine secretion.…”