Synaptic depression and the kinetics of exocytosis in retinal bipolar cells

The capacitance technique was used to investigate exocytosis at the ribbon synapse of depolarizing bipolar cells from the goldfish retina. When the Ca(2+) current was activated strongly, the rapidly releasable pool of vesicles (RRP) was released with a single rate-constant of approximately 300-500 sec(-1). However, when the Ca(2+) current was activated weakly by depolarization in the physiological range (-45 to -25 mV), exocytosis from the RRP occurred in two phases. After the release of 20% or more of the RRP, the rate-constant of exocytosis fell by a factor of 4-10. Thus, synaptic depression was caused by a reduced sensitivity to Ca(2+) influx, as well as simple depletion of the RRP. In the resting state, the rate of exocytosis varied with the amplitude of the Ca(2+) current raised to the power of 2. In the depressed state, the sensitivity to Ca(2+) influx was reduced approximately fourfold. The initial phase of exocytosis accelerated e-fold for every 2.1 mV depolarization over the physiological range and averaged 120 sec(-1) at -25 mV. The synapse of depolarizing bipolar cells therefore responds to a step depolarization in a manner similar to a high-pass filter. This transformation appears to be determined by the presence of rapidly releasable vesicles with differing sensitivities to Ca(2+) influx. This might occur if vesicles were docked to the plasma membrane at different distances from Ca(2+) channels. These results suggest that the ribbon synapse of depolarizing bipolar cells may be a site of adaptation in the retina.