Increased Ca2+ influx through Na+/Ca2+ exchanger during long-term facilitation at crayfish neuromuscular junctions.

Intense motor neuron activity induces a long-term facilitation (LTF) of synaptic transmission at crayfish neuromuscular junctions (NMJs) that is accompanied by an increase in the accumulation of presynaptic Ca2+ ions during a test train of action potentials. It is natural to assume that the increased Ca2+ influx during action potentials is directly responsible for the increased transmitter release in LTF, especially as the magnitudes of LTF and increased Ca2+ influx are positively correlated. However, our results indicate that the elevated Ca2+ entry occurs through the reverse mode operation of presynaptic Na+/Ca2+ exchangers that are activated by an LTF-inducing tetanus. Inhibition of Na+/Ca2+ exchange blocks this additional Ca2+ influx without affecting LTF, showing that LTF is not a consequence of the regulation of these transporters and is not directly related to the increase in [Ca2+]i reached during a train of action potentials. Their correlation is probably due to both being induced independently by the strong [Ca2+]i elevation accompanying LTF-inducing stimuli. Our results reveal a new form of regulation of neuronal Na+/Ca2+ exchange that does not directly alter the strength of synaptic transmission.