Adrenaline stimulates glucagon secretion in pancreatic A-cells by increasing the Ca2+ current and the number of granules close to the L-type Ca2+ channels.
We have monitored electrical activity, voltage-gated Ca2+ currents, and exocytosis in single rat glucagon-secreting pancreatic A-cells. The A-cells were electrically excitable and generated spontaneous Na+- and Ca2+-dependent action potentials. Under basal conditions, exocytosis was tightly linked to Ca2+ influx through omega-conotoxin-GVIA-sensitive (N-type) Ca2+ channels. Stimulation of the A-cells with adrenaline (via beta-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 Ca2+ influx through L-type Ca2+ 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 Ca2+ channels.
Gromada
J
J
Department of Islet Cell Physiology, Novo Nordisk A/S, The Symbion Science Park, DK-2100 Copenhagen. JLG@novo.dk
Bokvist
K
K
Ding
W G
WG
Barg
S
S
Buschard
K
K
Renström
E
E
Rorsman
P
P
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004553:Electric Conductivity; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011917:Rats, Inbred Lew; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D005934:Glucagon; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D002118:Calcium; D004837:Epinephrine