Regulation of synaptic transmission by mitochondrial ion channels.
Mitochondria are abundant within neuronal presynaptic terminals, where they provide energy for sustained neurotransmitter secretion. Injection of Bcl-xL protein into squid giant presynaptic terminal potentiates neurotransmitter release, while a naturally occurring, proteolytic fragment of BCL-xL causes rundown of synaptic function. The cleaved form of BCL-xL generates large, multiconductance ion channel activity in synaptic mitochondrial outer membranes. A rapid onset of synaptic rundown can also be produced by depriving the synapse of oxygen, and hypoxia also induces large channel activity in mitochondrial outer membranes. Channel activity induced by cleaved BCL-xL or by hypoxia is attenuated by NADH, an inhibitor of the voltage-dependent anion channel (VDAC) of mitochondrial outer membranes. Finally, the large conductances elicited by hypoxia are prevented by the addition of a protease inhibitor that prevents cleavage of BCL-xL. The opposing activities of BCL-xL and its proteolytic fragment may regulate the release of ATP from mitochondria during synaptic transmission.
Jonas
Elizabeth
E
Department of Internal Medicine (Endocrinology), Yale University School of Medicine, 333 Cedar St., PO Box 208020, New Haven, Connecticut 06520, USA. elizabeth.jonas@yale.edu
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D049832:Decapodiformes; D004553:Electric Conductivity; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D018272:Porins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D050994:Voltage-Dependent Anion Channels; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D007473:Ion Channels; D024101:Mitochondrial Proteins; D018272:Porins; D019253:Proto-Oncogene Proteins c-bcl-2; D050994:Voltage-Dependent Anion Channels; D051020:bcl-X Protein