Inhibitors of calcium buffering depress evoked transmitter release at the squid giant synapse.
Evoked release of transmitter at the squid giant synapse was examined under conditions where the calcium ion concentration in the presynaptic terminal was manipulated by inhibitors of calcium sequestration. Simultaneous intracellular recordings of presynaptic and post-synaptic resting and action potentials were made during bath application of one of the following metabolic inhibitors: sodium cyanide (NaCN), carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP); ruthenium red (RuR) and sodium-free (lithium) sea water. Cyanide and lithium sea water reversibly depressed the post-synaptic potential (p.s.p.) whilst RuR and FCCP blocked the evoked post-synaptic response irreversibly. The progressive reduction of p.s.p. amplitude was accompanied by a reversible increase in synaptic delay. The time course of block of the p.s.p. was similar for different agents and dependent on the rate of presynaptic activity (30-40 min at 0.01 Hz). Recovery of the post-synaptic action potential following block by cyanide and lithium sea water was obtained within 40 min and 5 min respectively. Synaptic depression by the metabolic inhibitors does not result from changes in presynaptic resting or action potentials, nor from a change in post-synaptic receptor sensitivity. The post-synaptic response to the local ionophoresis of L-glutamate was unchanged following inhibition of evoked release of transmitter by cyanide. Injections of EGTA into presynaptic terminals poisoned by cyanide produced transient increases in p.s.p. amplitude, suggesting that cyanide is having its effect through raising intracellular calcium rather than lowering ATP. Control experiments injecting EGTA into unpoisoned nerve terminals showed no apparent effect on evoked transmitter release.
D J
DJ
Adams
K
K
Takeda
J A
JA
Umbach
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D049832:Decapodiformes; D004533:Egtazic Acid / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012430:Ruthenium Red / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D005971:Glutamates; D018377:Neurotransmitter Agents; D012430:Ruthenium Red; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D018698:Glutamic Acid; D004533:Egtazic Acid; D008094:Lithium; D012966:Sodium Cyanide; D002118:Calcium