Paired-pulse facilitation of transmitter release at different levels of extracellular calcium concentration.

High-frequency synaptic activity can cause facilitation of transmitter release due to accumulation of "residual Ca(2+)" at the nerve terminal. However, the mechanism of this phenomenon is still under debate. Here we show that, using extracellular recording from frog cutaneous pectoris muscle, paired-pulse facilitation (PPF) at the frog neuro-muscular junction decays in two or three-exponential manner depending upon the extracellular Ca(2+) concentration ([Ca(2+)](e)). First, second and "early" PPF components are analyzed and described in this study. Considering the dependence of PPF on [Ca(2+)](e), existence of several specific high-affinity intra-terminal Ca(2+)-binding sites that underlie the facilitation of transmitter release at the frog neuro-muscular junction is proposed.