title: Prolonged time course of glutamate release from nerve terminals: relationship between stimulus duration and the secretory event.
abstract: The kinetics of synaptosomal [3H]glutamate release were measured on a subsecond time scale to study the relationship between the length of depolarization and the duration of the secretory event. The time course of release evoked by elevated K+ was complex, proceeding for several seconds after a 200-ms depolarization. We developed a protocol for depolarizing excitable membranes on a millisecond time scale to deliver brief depolarizations, termed the synthetic action potential, by using batrachotoxin to activate Na+ channels. Depolarization is achieved by superfusing with solutions containing elevated concentrations of Na+, and the duration of the depolarization is limited by including tetrodotoxin (TTX) in the superfusion solution to block Na+ current and membrane depolarizations were made in batrachotoxin-treated sensory neurons using patch clamp recording methods. Rapid increases in Na+ and TTX concentrations produced transient increases in inward Na+ current that decayed with a time course proportional to TTX concentration. Current clamp measurements indicated that, with 10 microM TTX, depolarizations last approximately 30 ms. Nonetheless, synaptosomal release of [3H]glutamate triggered by the synthetic action potential remained prolonged. Brief neuronal action potentials at some synapses may trigger transmitter release that persists for several seconds.
authors.affiliation: Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Turner
authors.forename: K
authors.initials: K
authors.lastname: Dunlap
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005625:Frontal Lobe / Q000648:ultrastructure; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D009411:Nerve Endings / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium
chemical_list: D001496:Batrachotoxins; D015222:Sodium Channels; D014316:Tritium; D018698:Glutamic Acid; D013779:Tetrodotoxin; D011189:Potassium Chloride; D012964:Sodium; D015761:4-Aminopyridine; D002118:Calcium