Parallel oscillations of intracellular calcium activity and mitochondrial membrane potential in mouse pancreatic B-cells.
Insulin secretion in normal B-cells is pulsatile, a consequence of oscillations in the cell membrane potential (MP) and cytosolic calcium activity ([Ca(2+)](c)). We simultaneously monitored glucose-induced changes in [Ca(2+)](c) and in the mitochondrial membrane potential DeltaPsi, as a measure for ATP generation. Increasing the glucose concentration from 0.5 to 15 mM led to the well-known hyperpolarization of DeltaPsi and ATP-dependent lowering of [Ca(2+)](c). However, as soon as [Ca(2+)](c) rose due to the opening of voltage-dependent Ca(2+) channels, DeltaPsi depolarized and thereafter oscillations in [Ca(2+)](c) were parallel to oscillations in DeltaPsi. A depolarization or oscillations of DeltaPsi cannot be evoked by a substimulatory glucose concentration, but Ca(2+) influx provoked by 30 mM KCl was followed by a depolarization of DeltaPsi. The following feedback loop is suggested: Glucose metabolism via mitochondrial ATP production and closure of K(+)(ATP) channels induces an increase in [Ca(2+)](c). The rise in [Ca(2+)](c) in turn decreases ATP synthesis by depolarizing DeltaPsi, thus transiently terminating Ca(2+) influx.
Krippeit-Drews
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Department of Pharmacology, University of Tübingen, Auf der Morgenstelle 8, Tübingen, D-72076, Germany. peter.krippeit-drews@uni-tuebingen.de
Düfer
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Drews
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009991:Oscillometry; D019810:Sodium Azide / Q000494:pharmacology
D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D019810:Sodium Azide; D005947:Glucose; D002118:Calcium