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Effects of Diltiazem on Bioenergetics, K + Gradients, and Free Cytosolic Ca 2+ Levels in Rat Brain Synaptosomes Submitted to Energy Metabolism Inhibition and Depolarization
Author(s) -
Dagani F.,
Feletti F.,
Canevari L.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb08528.x
Subject(s) - veratridine , phosphocreatine , depolarization , diltiazem , chemistry , synaptosome , membrane potential , biophysics , ouabain , rotenone , ionomycin , biochemistry , medicine , endocrinology , calcium , biology , sodium , intracellular , mitochondrion , membrane , energy metabolism , sodium channel , organic chemistry
Abstract: Diltiazem was able to decrease the oxygen consumption rate and lactate production in synaptosomes isolated from rat forebrains, both under control and depolarized (40 μM veratridine) conditions, starting from a concentration of 250 μ M. This effect was particularly evident when synaptosomes were depolarized by veratridine. This depolarization‐counteracting action was evident also when transplasma membrane K + diffusion potentials were measured after depolarization induced by veratridine and by rotenone with a glucose shortage. The concentrations of ATP, phosphocre‐atine, and creatine were less sensitive to diltiazem action. The concentration/response relationships were the same as those found for the oxygen consumption rate, lactate production, and K + diffusion potentials. The effects of 0.5 m M diltiazem in counteracting inhibition of energy metabolism induced by rotenone without glucose were no longer detectable when either Ca 2+ or Na + was absent from the incubation medium of synaptosomes. Diltiazem at the same concentrations (starting from 250 μ M) was able to inhibit both the veratridine‐induced and the rotenonc‐without‐glucose‐in‐duced increase in intrasynaptosomal free Ca 2+ levels evaluated with the fluorescent probe quin2. The results are discussed in view of a possible effect of diltiazem on voltage‐dependent Na + channels and the possibility of utilizing this approach for counteracting neuronal failure due to derangement of energy metabolism or hyperexcitation