Two components of transmitter release from the chick ciliary presynaptic terminal and their regulation by protein kinase C

1. A study was made of the effects of phorbol ester (phorbol 12-myristate 1 3-acetate, PMA, 0.1 mu M) on the two components of evoked transmitter relea se, namely the fast synchronous and the slow asynchronous components, from the giant presynaptic terminal of the chick ciliary ganglion. The excitator y postsynaptic currents (EPSCs) were recorded under whole cell voltage clam p of the postsynaptic neuron. 2. The decay time constant of the slow component was prolonged by replacing Ca2+ with Sr2+ In 5 mM [Sr2+](o) the fast component decayed with a time co nstant of 2.6 +/- 1.4 ms whereas the slow component decayed with a time con stant of 19 +/- 7 ms. 3. When stimulated with twin pulses with a short interpulse interval, the f ast component of the second EPSC was often depressed whereas the slow compo nent was usually facilitated. Both components were positively dependent on [Sr2+](o) in a,saturable manner, but the fast component approached its maxi mum at a lower [Sr2+](o) than the slow component. 4. PMA potentiated both the fast and slow components to a similar extent an d with a similar time course. For each component, the effect of PMA was les s potent at high [Sr2+](o) than at low [Sr2+](o). For either the fast or th e slow component the PMA-induced potentiation was accompanied by a reductio n in the paired-pulse ratio (PPR). 5. Despite the different dissociation constant for dextran-conjugated fura- 2, the fluorescent ratio for intraterminal [Sr2+] ([Sr2+](i)) decayed to th e baseline after the nerve-evoked increment with a time course similar to t hat for [Ca2+](i), suggesting that intraterminal Sr2+ is buffered less effi ciently than Ca2+. PMA did not increase the [Sr2+](i) transients: produced by stimulation of the presynaptic oculomotor nerve. 6. It is suggested that protein kinase C (PKC) modulates both the fast and slow components through common molecular mechanisms that upregulate the Sr2 + sensitivity of the vesicle fusion probability.