Article

Interplay between sodium and calcium dynamics in granule cell presynaptic terminals.

Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Biophysical Journal (impact factor: 3.65). 12/1997; 73(5):2476-88. DOI:10.1016/S0006-3495(97)78276-6 pp.2476-88
Source: PubMed

ABSTRACT 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 approximately 10% of peak levels with tau approximately 100 ms, to approximately 1% of peak values with tau approximately 6 s, and then returned to prestimulus levels with tau approximately 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.

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Keywords

calcium ATPase
 
double exponential decay
 
Fluorescent indicators
 
granule cell parallel fibers
 
intracellular sodium
 
large concomitant sodium influx
 
peak levels
 
phases
 
plasma membrane
 
prestimulus levels
 
presynaptic boutons
 
presynaptic levels
 
prevented calcium entry
 
rapid component
 
rapid phase
 
resting levels
 
slow return
 
sodium entry
 
sodium/calcium exchanger
 
time constants