Stimulation-dependent depression of readily releasable neurotransmitter pools in brain.

Previously accumulated GABA was released from isolated forebrain synaptosomes with repeated calcium stimulation in elevated-potassium medium. Fractional release (calcium-dependent) in response to a second calcium pulse (90-120 sec later) was depressed to approximately 60% of initial release. Neither initial GABA release nor the subsequent depression of release was affected by variations in the labelling duration. Stimulation-dependent depression of labelled GABA and norepinephrine release was demonstrated from both cerebral cortex and cerebellum synaptosomal preparations. In addition, depression resulted from prior stimulation in the presence of veratridine, A23187 or elevated-potassium. Although release of previously accumulated GABA was depressed by calcium stimulation, the release of GABA accumulated between stimulations was not. Release of this recently accumulated GABA was indistinguishable from the initial release of previously accumulated GABA and larger than the subsequently depressed release from the previously accumulated pools. These data imply (1) that the depressed release resulted from a decrease of available transmitter in pools that support secretion processes, (2) that depressed release did not result from a depression of stimulus-secretion coupling processes, and (3) that transmitter accumulated subsequent to release events is released preferentially to transmitter accumulated prior to the intervening stimulation.