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The Calmodulin Antagonists, Trifluoperazine and R24571, Depolarize the Mitochondria Within Guinea Pig Cerebral Cortical Synaptosomes

1984; Wiley; Volume: 42; Issue: 6 Linguagem: Inglês

10.1111/j.1471-4159.1984.tb12741.x

1471-4159

R Snelling, David G. Nicholls,

Electrochemical Analysis and Applications

The effects of trifluoperazine and 1-[bis(p-chlorophenyl)methyl]-3-[2, 4-dichloro-beta-(2,4- dichlorobenzyloxy )phenethyl]imidazolium chloride ( R2457 ) upon synaptosomal calcium transport, plasma membrane potential, in situ mitochondrial membrane potential, and ATP levels are investigated in order to assess the suitability of these calmodulin antagonists for investigating calmodulin-dependent processes in the nerve terminal. Both agents appear to act selectively at the mitochondrial membrane, causing extensive depolarization at concentrations in excess of 10 microM (trifluoperazine) or 0.5 microM ( R2457 ). The extent of Ca uptake into the synaptosomes is decreased, consistent with the loss of the mitochondrial compartment. There is no inhibition of the efflux of Ca from the synaptosomes. Depolarization-dependent Ca uptake is not prevented by R24571 . Synaptosomal ATP levels decrease to an extent consistent with the collapse of the mitochondrial potential. It is concluded that the uncoupling effect of these agents on the in situ mitochondria prevents their being used to investigate the role of calmodulin in intact synaptosomes.