Differential regulation of transmitter release by presynaptic and glial Ca2+ internal stores at the neuromuscular synapse.

The differential regulation of synaptic transmission by internal Ca(2+) stores of presynaptic terminals and perisynaptic Schwann cells (PSCs) was studied at the frog neuromuscular junction. Thapsigargin (tg), an inhibitor of Ca(2+)-ATPase pumps of internal stores, caused a transient Ca(2+) elevation in PSCs, whereas it had no effect on Ca(2+) stores of presynaptic terminals at rest. Tg prolonged presynaptic Ca(2+) responses evoked by single action potentials with no detectable increase in the resting Ca(2+) level in nerve terminals. However, Ca(2+) accumulation was observed during high frequency stimulation. Tg induced a rapid rise in endplate potential (EPP) amplitude, accompanied by a delayed and transient increase. The effects appeared presynaptic, as suggested by the lack of effects of tg on the amplitude and time course of miniature EPPs (MEPPs). However, MEPP frequency was increased when preparations were stimulated tonically (0.2 Hz). The delayed and transient increase in EPP amplitude was occluded by injections of the Ca(2+) chelator BAPTA into PSCs before tg application, whereas a rise in intracellular Ca(2+) in PSCs induced by inositol 1,4,5-triphosphate (IP(3)) injections potentiated transmitter release. Furthermore, increased Ca(2+) buffering capacity after BAPTA injection in PSCs resulted in a more pronounced synaptic depression induced by high frequency stimulation of the motor nerve (10 Hz/80 sec). It is concluded that presynaptic Ca(2+) stores act as a Ca(2+) clearance mechanism to limit the duration of transmitter release, whereas Ca(2+) release from glial stores initiates Ca(2+)-dependent potentiation of synaptic transmission.