Role of voltage-dependent ionic currents in coupling glucose stimulation to insulin secretion in canine pancreatic islet B-cells.
Glucose-induced electrical activity in canine pancreatic islet B cells is distinct from that in rodent islets, though both display Ca(2+)-dependent insulin secretion. Rodent islet B cells undergo regular bursts of Ca(2+)-dependent action potentials, while canine islet B cells generate isolated Na(+)-dependent action potentials which often give way to a plateau depolarization. Here we present evidence to reconcile the species difference in electrical activity with the similarity of Ca2+ dependence of secretion. (i) In canine B cells increasing glucose concentrations produce membrane depolarization and increasing frequency of Nao-dependent action potentials until a background membrane potential (approximately -40 mV) is reached where Na+ currents are inactivated. (ii) Voltage-dependent Ca2+ currents are present which are activated over the voltage excursion of the action potential (-50 to +20 mV) and inactivate slowly, (over seconds) in the range of the plateau depolarization (-40 to -25 mV). Hence, they are available to contribute to both phases of depolarization. (iii) Tetrodotoxin (TTX) reduces by half an early transient phase of glucose-stimulated insulin secretion but not a subsequent prolonged plateau phase. The transient phase of secretion often corresponds well in time to the period of initial high frequency action potential activity. These latter results suggest that in canine B cells voltage-dependent Na+ and Ca2+ currents mediate biphasic glucose-induced insulin secretion. The early train of Na(+)-dependent action potentials, by transiently activating Ca2+ channels and allowing pulsatile Ca2+ entry, may promote an early transient phase of insulin secretion. The subsequent sustained plateau depolarization, by allowing sustained Ca2+ entry, may permit steady insulin release.
Pressel
D M
DM
Department of Medicine (Jewish Hospital), Washington University Medical Center, St. Louis, Missouri 63110.
Misler
S
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D007328:Insulin; D012964:Sodium; D005947:Glucose; D011188:Potassium; D002118:Calcium