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PMID: 9370441 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Biophysical journal ·Vol. 73 ·No. 5 ·1997-11-00 ·Pages 2476-88

Regehr WG

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.

MeSH Terms
Animals Cadmium/pharmacology Calcium/metabolism Calcium-Transporting ATPases/metabolism Cell Membrane/metabolism Cerebellum/metabolism Electric Stimulation Electrophysiology Fluorescent Dyes Fluorometry Fura-2/analogs & derivatives,metabolism In Vitro Techniques Kinetics Models, Biological Presynaptic Terminals/metabolism Rats Rats, Sprague-Dawley Sodium/metabolism Sodium-Calcium Exchanger/metabolism
Chemicals
Fluorescent Dyes Sodium-Calcium Exchanger mag-Fura 5 Cadmium Sodium Calcium-Transporting ATPases Calcium Fura-2
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Regehr W G
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. [email protected]
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
Published
1997-11-00
Pages
2476-88
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1181149
Subset
IM
Grants
NINDS NIH HHS · R01-NS32405-01 · United States
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