抄録
The efficacy of synaptic transmission is determined by the quantal parameters such as the number of readily releasable pool vesicles (N), release probability (p) and postsynaptic response to a single quantum of transmitter (q). After massive vesicle exocytosis, N is replenished by vesicle trafficking for maintaining synaptic efficacy. However the mechanism underlying vesicle dynamics remains unknown. As a first step, we investigated whether staurosporine, a general kinase inhibitor, affects quantal parameters at the calyx of Held synapse in the brainstem slices of 12- to 15-day-old rats. Pretreatment of slices with 2 μM staurosporine for 1h decreased the amplitude of evoked EPSCs and slowed their rise time, but had no effect on their decay time. Staurosporine also reduced the frequency of spontaneous miniature EPSCs without affecting their amplitude (q) or kinetics. Estimation of quantal parameters, using the tetanic stimulation protocol, revealed that staurosporine reduced Nq, but not p. Staurosporine increased the magnitude of synaptic depression during repetitive stimulation (1-100 Hz) supporting the depletion model of synaptic depression. Staurosporin slowed recovery from depression caused by 10-100 Hz-stimulation without affecting the fast phase of recovery time course after 100 Hz-stimulation. We conclude that staurosporine-sensitive protein kinases affect the size of readily releasable pool and specifically accelerate a slow component of vesicle mobilization thereby contributing to the replenishment of readily releasable vesicles. [J Physiol Sci. 2006;56 Suppl:S162]
