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Role of sodium-calcium exchange in regulation of intracellular calcium in nerve terminals

Journal Article · · Am. J. Physiol.; (United States)
OSTI ID:6862511
Ca efflux from rat brain presynaptic nerve terminals (synaptosomes) was examined after loading the terminals with /sup 45/Ca during a brief depolarization, usually in media containing 20 ..mu..M Ca labeled with /sup 45/Ca, to assure a small (physiological) load. Efflux of /sup 45/Ca was very slow in the absence of external Na and Ca and was greatly accelerated by Na and/or Ca. The dependence of /sup 45/Ca efflux on external Na was sigmoid, with a Hill coefficient of approx. 4.5; this implies that more than two external Na ions are required to activate the efflux of one Ca ion. The external Na (Na/sub 0/)-dependent Ca efflux was inhibited by 1 mM external La, by low temperature, and by raising external K. With small Ca loads, the mitochondrial uncoupler, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), had negligible effect on either Ca uptake or efflux; with large loads, however, FCCP reduced the depolarization-stimulated Ca uptake and increased the Na/sub 0/-dependent Ca efflux. These effects may be attributed to reduction of mitochondrial Ca sequestration. Mitochondria do not appear to sequester much Ca when the loads are smaller. Estimations of Ca efflux indicate that approx. 20% of a small /sup 45/Ca load may be extruded via Na/sup +/-Ca/sup 2 +/ exchange within 1 s; this corresponds to a net Ca efflux of approx. 110 pmol Ca x mg protein/sup -1/ x s/sup -1/. This rate of extrusion is equivalent to the net Ca gain when the terminals fire at a frequency of approx. 18/s. The data on the Ca efflux into Na- and Ca-free media indicate that the ATP-fueled Ca pump can only extrude approx. 10-20 pmol Ca x mg protein/sup -1/ x s/sup -1/. Thus the results imply that Na/sup +/-Ca/sup 2 +/ exchange plays an important role in helping to extrude the Ca that enters during activity.
Research Organization:
Univ. of Maryland School of Medicine, Baltimore (USA)
OSTI ID:
6862511
Journal Information:
Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 252:6; ISSN AJPHA
Country of Publication:
United States
Language:
English