Phosphate depletion increases cytosolic calcium of brain synaptosomes

Abstract

Phosphate depletion (PD) is associated with a rise in resting levels of [Ca2+]i in pancreatic islets. It is not known whether this derangement occurs in other cells, and the mechanisms by which PD affects [Ca2+]i have not been delineated. This study examined the effect of PD on [Ca2+]i of brain synaptosomes and evaluated potential mechanisms that may lead to rise in their [Ca2+]i. [Ca2+]i levels in synaptosomes of PD rats (460 +/- 18.3 nM) were higher (P less than 0.01) than those of pair-weighed (PW) rats (358 +/- 12.5 nM). Verapamil treatment of PD rats (PD-V) normalized [Ca2+]i in their synaptosomes (361 +/- 8.5 nM). In verapamil-treated PW rats (PW-V), synaptosomal [Ca2+]i (359 +/- 8.3 nM) was not affected. ATP content and Na(+)-K(+)-ATPase activity of synaptosomes were lower (P less than 0.01) in PD rats than in PW, PD-V, and PW-V rats. The values of these parameters from the latter three groups were not different. Km of synaptosomal Ca2(+)-ATPase was not affected by PD but Vmax of this enzyme (2.5 +/- 0.33 mumol Pi.mg protein-1.h-1) was lower (P less than 0.05) than in PW (5.4 +/- 0.66 mumol Pi.mg protein-1.h-1), PD-V, and PW-V rats. Our data indicate that PD raises [Ca2+]i in brain synaptosomes and suggest that PD increases calcium entry into synaptosomes. This would inhibit mitochondrial ATP production, with a consequent fall in ATP content of synaptosomes.(ABSTRACT TRUNCATED AT 250 WORDS)