Interplay between sodium and calcium dynamics in granule cell presynaptic terminals

Fluorescent indicators were used to detect stimulus-evoked changes in presynaptic levels of intracellular sodium (Na-i) and calcium (Ca-i) in granule cell parallel fibers in brain slices from rat cerebellum. Ca-i increased during stimulation, and three exponentials were needed to approximate its return to prestimulus levels. Ca-i decayed to similar to 10% of peak levels with tau similar to 100 ms, to similar to 1% of peak values with tau similar to 6 s, and then returned to prestimulus levels with tau similar to 1-2 min, After stimulation, Na-i accumulated in two phases; one rapid, the other continuing for several hundred milliseconds, The return of Na-i to prestimulus levels was well approximated by a double exponential decay with time constants of 6-17 s and 2-3 min, Manipulations that prevented calcium entry eliminated both the slow component of sodium entry and the rapid component of Na-i decay. Reductions of extracellular sodium slowed the rapid phase of Ca-i decay. These Ca-i and Na-i transients were well described by a model in which the plasma membrane of presynaptic boutons contained both a sodium/calcium exchanger and a calcium ATPase (Ca-ATPase), According to this model, immediately after stimulation the sodium/calcium exchanger removes calcium from the terminal more rapidly than does the Ca-ATPase. Eventually, the large concomitant sodium influx brings the exchanger into steady-state, leaving only the Ca-ATPase to remove calcium, This perturbs the equilibrium of the sodium/calcium exchanger, which opposes the Ca-ATPase, leading to a slow return of Ca-i and Na-i to resting levels.