The Combined Effect of Glucose and β-Hydroxybutyrate on the Membrane Potential of Synaptosomal Mitochondria

—The ketogenic diet is used as a treatment for different brain diseases. It involves replacement of dietary carbohydrates with fat, which leads to production of ketone bodies, predominantly β-hydroxybutyrate. The mechanism of the protective effect of the ketogenic diet remains poorly studied. In this work, the combined influence of glucose and β-hydroxybutyrate on the potentials of the synaptosomal plasma membrane and the mitochondrial membrane was investigated. It was found that the presence of ketone bodies in a glucose-containing incubation medium did not affect the synaptosomal plasma membrane potential, in contrast to what was previously observed for the neuronal plasma membrane. It was shown that incubation of synaptosomes in the medium containing only β-hydroxybutyrate resulted in mitochondrial depolarization (ΔΨ change). At the same time, the presence of ketone bodies in the glucose-containing incubation medium led to mitochondrial hyperpolarization. The observed depolarization was partially compensated by an increase in mitochondrial ΔpH, which was induced by mitochondrial depolarization as such, but not by the presence of β-hydroxybutyrate. Thus, ketone bodies can be utilized by synapses as energy substrates, but β-hydroxybutyrate is a less effective energy source than glucose.