Depression of transmitter release at synapses in the rat superior cervical ganglion: the role of transmitter depletion.

The characteristics of depression of the excitatory postsynaptic potential (EPSP) during a short train of impulses to the rat superior cervical ganglion (SCG) have been ascertained with the object of determining the relative contributions of transmitter depletion and autoreceptors to depression. Successive EPSPs in a short train were depressed after the first (Vo) up to about the fourth impulse when a steady-state depressed EPSP level (Vss) was reached. Vss increased with the stimulation frequency between 1 and 30 Hz. Vo recovered after a short train with a time constant of about 2.8 s in the frequency range from 5 to 30 Hz. In order to determine if depression was related to changes in calcium influx with successive impulses in the train. preganglionic boutons were loaded with the calcium indicator Oregon Green 488 BAPTA-1 and line scans taken through individual boutons with a confocal laser microscope. Successive calcium transients were of about the same amplitude in boutons during short trains of impulses at 5 Hz. The contribution of autoreceptors activated by the action of endogenously derived adenosine on the extent of depression of the EPSP during short trains was ascertained by blocking these receptors with 8-phenyltheophylline (10 microM). There was no change in the extent or time course of development of depression. Similar results were obtained with the opioid receptor antagonist naloxone (10 microM) and the adrenergic receptor antagonist yohimbine (10 microM). Factors, which increased the extent of transmitter release during a train, such as increasing the external calcium concentration from 0.8 to 2.5 mM, increased depression. Factors. which decreased the extent of transmitter release such as increasing the exogenous adenosine concentration between 1 and 200 microM decreased depression. These results are interpreted in terms of a model in which vesicles are mobilised by a calcium-dependent process from a store into an available pool of docked vesicles. Depletion of the docked vesicles during exocytosis then leads to depression of transmitter release during a train of impulses.