Abstract
Activity-dependent modulation of synaptic transmission is an essential mechanism underlying many brain functions. Here we report an unusual form of synaptic modulation that depends on Na+ influx and mitochondrial Na(+)-Ca2+ exchanger, but not on Ca2+ influx. In Ca(2+)-free medium, tetanic stimulation of Xenopus motoneurons induced a striking potentiation of transmitter release at neuromuscular synapses. Inhibition of either Na+ influx or the rise of Ca2+ concentrations ([Ca2+]i) at nerve terminals prevented the tetanus-induced synaptic potentiation (TISP). Blockade of Ca2+ release from mitochondrial Na(+)-Ca2+ exchanger, but not from ER Ca2+ stores, also inhibited TISP. Tetanic stimulation in Ca(2+)-free medium elicited an increase in [Ca2+]i, which was prevented by inhibition of Na+ influx or mitochondrial Ca2+ release. Inhibition of PKC blocked the TISP as well as mitochondrial Ca2+ release. These results reveal a novel form of synaptic plasticity and suggest a role of PKC in mitochondrial Ca2+ release during synaptic transmission.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Animals
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Calcium / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
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Chelating Agents / pharmacology
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Enzyme Inhibitors / pharmacology
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Intracellular Fluid / drug effects
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Intracellular Fluid / metabolism
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Neuromuscular Junction / drug effects
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Neuromuscular Junction / metabolism*
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Sodium / metabolism
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Sodium Channel Blockers / pharmacology
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Sodium Channels / drug effects
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Sodium Channels / metabolism
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Sodium-Calcium Exchanger / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Xenopus
Substances
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Chelating Agents
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Enzyme Inhibitors
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Sodium Channel Blockers
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Sodium Channels
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Sodium-Calcium Exchanger
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Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
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Sodium
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Protein Kinase C
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Calcium