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The Journal of Neuroscience, December 15, 2001, 21(24):9598-9607
Roles for Mitochondrial and Reverse Mode Na+/Ca2+ Exchange and the Plasmalemma Ca2+ ATPase in Post-Tetanic Potentiation at Crayfish Neuromuscular Junctions
Ning Zhong, Vahri Beaumont, and Robert S. Zucker Department of Molecular and Cell Biology, University of California, Berkeley, California, 94720-3200
We have explored the processes regulating presynaptic calcium concentration ([Ca2+]i) in the generation of post-tetanic potentiation (PTP) at crayfish neuromuscular junctions, using spectrophotometric dyes to measure changes in [Ca2+]i and [Na+]i and effects of inhibitors of Ca2+-transport processes. The mitochondrial Na+/Ca2+ exchange inhibitor CGP 37157 was without effect, whereas the reverse mode plasmalemmal Na+/Ca2+ exchange inhibitor KB R7943 reduced PTP and Ca2+ accumulation caused by increased [Na+]i. Exchange inhibitory peptide and C28R2 had opposite effects, consistent with their block of the plasma membrane Ca2+ ATPase. All drugs except CGP 37157 reduced Ca2+ accumulation caused by Na+ accumulation, which occurred on block of the Na+/K+ pump, acting in proportion to their effects on plasmalemmal Na+/Ca2+ exchange. We find no role for mitochondrial Na+/Ca2+ exchange in presynaptic Ca2+ regulation. The plasma membrane Na+/Ca2+ exchanger acts in reverse mode to admit Ca2+ into nerve terminals during and for some minutes after tetanic stimulation, while at the same time the plasma membrane Ca2+ ATPase operates as an important Ca2+ removal process. The interplay of these two Ca2+ transport processes with Na+-independent mitochondrial Ca2+ fluxes and the plasmalemma Na+/K+ pump determines the magnitude of tetanic [Ca2+]i accumulation and potentiation of excitatory transmission, and the post-tetanic time courses of decay of elevated [Ca2+]i and PTP.
Key words: post-tetanic potentiation; Na+/Ca2+ exchange; Ca2+ ATPase; mitochondria; transmitter release; crayfish; neuromuscular junction; synaptic transmission
Copyright © 2001 Society for Neuroscience 0270-6474/01/21249598-10$05.00/0
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