Adrenaline Stimulates Glucagon Secretion in Pancreatic A-Cells by Increasing the Ca(2+) Current and the Number of Granules Close to the L-Type Ca(2+) Channels

We have monitored electrical activity, voltage-gated Ca(2+) currents, and exocytosis in single rat glucagon-secreting pancreatic A-cells. The A-cells were electrically excitable and generated spontaneous Na(+)- and Ca(2+)-dependent action potentials. Under basal conditions, exocytosis was tightly linked to Ca(2+) influx through ω-conotoxin-GVIA–sensitive (N-type) Ca(2+) channels. Stimulation of the A-cells with adrenaline (via β-adrenergic receptors) or forskolin produced a greater than fourfold PKA-dependent potentiation of depolarization-evoked exocytosis. This enhancement of exocytosis was due to a 50% enhancement of Ca(2+) influx through L-type Ca(2+) channels, an effect that accounted for <30% of the total stimulatory action. The remaining 70% of the stimulation was attributable to an acceleration of granule mobilization resulting in a fivefold increase in the number of readily releasable granules near the L-type Ca(2+) channels.