Arachidonic acid inhibits sodium currents and synaptic transmission in cultured striatal neurons.
In the striatum, dopamine generates arachidonic acid (AA) and induces synaptic depression. Here, we report that Na+ channels are a target for AA in both cultured and acutely isolated striatal neurons. AA depressed veratrine-induced Na+ influx and neurotransmitter release. Whole-cell voltage clamp revealed that peak Na+ currents are depressed, and steady-state inactivation shifts -15 mV in the presence of AA. Furthermore, inactivation was accelerated, and recovery from inactivation was delayed. These actions of AA were not produced by AA metabolites or protein kinase C activation. In addition, AA reduced both the amplitude and frequency of action potentials and depressed spontaneous inhibitory postsynaptic currents without affecting miniature inhibitory postsynaptic currents. These data suggest that AA modulates presynaptic, Na(+)-dependent action potentials, thereby contributing to striatal synaptic depression.
Fraser
D D
DD
Neuroscience Research Group, University of Calgary, Alberta, Canada.
Hoehn
K
K
Weiss
S
S
MacVicar
B A
BA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D004594:Electrophysiology / Q000379:methods; D004622:Embryo, Mammalian; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014702:Veratrine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D026941:Sodium Channel Blockers; D016718:Arachidonic Acid; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D011494:Protein Kinases; D014702:Veratrine; D002118:Calcium