High external Ca2+ levels trigger membrane potential oscillations in mouse pancreatic beta-cells during blockade of K(ATP) channels.
Glucose depolarizes the pancreatic beta-cell and induces membrane potential oscillations, but the nature of the underlying oscillatory conductance remains unknown. We have now investigated the effects of the Ca2+ ionophore ionomycin and high external Ca2+ concentration ([Ca2+]o) on glucose-induced electrical activity and whole islet intracellular free Ca2+ concentration ([Ca2+]i), under conditions where the K(ATP) channel was blocked (100 microM tolbutamide or 4 microM glibenclamide). Raising [Ca2+]o to 10.2 or 12.8 mM, but not to 5.1 or 7.7 mM, turned continuous electrical activity into bursting activity. High [Ca2+]o (12.8 mM) regenerated a pattern of fast [Ca2+]i oscillations overshooting the levels recorded in tolbutamide. Ionomycin (10 microM) raised the [Ca2+]i and synergized with 5.1 mM Ca2+ to hyperpolarize the beta-cell membrane. The data indicate that a [Ca2+]i-sensitive and sulphonylurea-insensitive oscillatory conductance underlies the beta-cell bursting activity.
Santos
R M
RM
Center for Neurosciences of Coimbra, Department of Zoology, University of Coimbra, Portugal.
Barbosa
R M
RM
Silva
A M
AM
Antunes
C M
CM
Rosario
L M
LM
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D005456:Fluorescent Dyes; D016257:Fura-2; D005905:Glyburide / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D014044:Tolbutamide / Q000494:pharmacology
D005456:Fluorescent Dyes; D015221:Potassium Channels; D015759:Ionomycin; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005905:Glyburide; D002118:Calcium; D016257:Fura-2