Barbiturates decrease voltage-dependent calcium conductance of mouse neurons in dissociated cell culture.
Barbiturates have been shown to reduce presynaptic release of neurotransmitter. It is likely that barbiturates alter transmitter release by decreasing calcium entry since barbiturates decrease calcium influx into synaptosomes and reduce the maximal rate of rise and duration of calcium-dependent action potentials. The mechanisms of barbiturate action on neuronal calcium entry have been studied using mouse dorsal root ganglion neurons in cell culture. Dorsal root ganglion neuron action potentials have a calcium-dependent component which is decreased by the barbiturates, pentobarbital (50-500 microM) and phenobarbital (500-2000 microM). Calcium-dependent action potential after hyperpolarization was also decreased by barbiturates. Intracellular injection of the potassium channel blocker, cesium, enhanced barbiturate actions. In voltage-clamp studies, barbiturates reduced inward calcium current and calcium chord conductance without altering the leak conductance which is present after all calcium conductance was blocked by application of cadmium ions (100 microM). Calcium current inactivation was accelerated by barbiturates but unaffected by cadmium. We conclude that barbiturates reduce calcium conductance by enhancing calcium channel inactivation or by producing open channel block of calcium channels.
M A
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Werz
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Macdonald
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D002586:Cesium / Q000378:metabolism; D005727:Ganglia, Spinal / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D001463:Barbiturates; D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D002586:Cesium; D013779:Tetrodotoxin; D012964:Sodium; D002118:Calcium