Phosphate depletion increases cytosolic calcium of brain synaptosomes
Massry, S.G.; Hajjar, S.M.; Koureta, P.; Fadda, G.Z.; Smogorzewski, M.
American Journal of Physiology 260(1 Pt 2): F12-F18
1991
ISSN/ISBN: 0002-9513 PMID: 1847011 Document Number: 372203
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 mechanism that may lead to rise in their [Ca2+]i. [Ca2+]i levels in synaptosomes of PD rats (460 .+-. 18.3 nM) were higher (P < 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 < 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 .mu.mol Pi.cntdot.mg protein-1.cntdot.h-1) was lower (P < 0.05) than in PW (5.4 .+-. 0.66 .mu.mol Pi.cntdot.mg protein-1.cntdot.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. Low ATP would impair Ca2+-ATPase and Na+K+-ATPase activity, resulting in reduced extrusion of calcium from synaptosomes and hence a rise in their [Ca2+]i. Verapamil, by blocking the enhanced calcium entry, prevents the rise in [Ca2+]i.