Presynaptic Terminals

Fluorescent indicators were used to detect stimulus-evoked changes in presynaptic levels of intracellular sodium (Na1) and calcium (Ca1) in granule cell parallel fibers in brain slices from rat cerebellum. Ca, increased during stimulation, and three exponentials were needed to approximate its return to prestimulus levels. Ca, decayed to -10% of peak levels with T 100 ms, to -1% of peak values with T 6 s, and then returned to prestimulus levels with T 1-2 min. After stimulation, Nai accumulated in two phases; one rapid, the other continuing for several hundred milliseconds. The return of Na, 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 Nai decay. Reductions of extracellular sodium slowed the rapid phase of Cai decay. These Ca, and Nai 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 Ca1 and Na1 to resting levels.