ROLE OF INTRACELLULAR CA2-INDUCED INCREASES IN TRANSMITTER RELEASE ATTHE FROG NEUROMUSCULAR-JUNCTION( IN STIMULATION)

Under conditions of reduced quantal content, repetitive stimulation of a presynaptic nerve can result in a progressive increase in the amoun t of transmitter released by that nerve in response to stimulation. At the frog neuromuscular junction, this increase in release has been at tributed to four different processes: first and second components of f acilitation, augmentation, and potentiation (e.g., Zengel, J. E., and K. L. Magleby. 1982. Journal of General Physiology. 80:583-611). It ha s been suggested that an increased entry of Ca2+ or an accumulation of intraterminal Ca2+ may be responsible for one or more of these proces ses. To test this hypothesis, we have examined the role of intracellul ar Ca2+ in mediating changes in end-plate potential (EPP) amplitude du ring and after repetitive stimulation at the frog neuromuscular juncti on. We found that increasing the extracellular Ca2+ concentration or e xposing the preparation to carbonyl cyanide m-chlorophenylhydrazone, i onomycin, or cyclopiazonic acid all led to a greater increase in EPP a mplitude during conditioning trains of 10-200 impulses applied at a fr equency of 20 impulses/s. These experimental manipulations, all of whi ch have been shown to increase intracellular levels of Ca2+, appeared to act by increasing primarily the augmentation component of increased release. The results of this study are consistent with previous sugge stions that the different components of increased release represent di fferent mechanisms, and that Ca2+ may be acting at more than one site in the nerve terminal.