Hyperpolarization induces a rise in intracellular sodium concentration in dopamine cells of the substantia nigra pars compacta

We investigated the effect of changes in membrane-voltage on intracellular sodium concentration (Na⁺]_i) of dopamine-sensitive neurons of the substantia nigra pars compacta in a slice preparation of rat mesencephalon. Whole-cell patch-clamp techniques were combined with microfluorometric measurements of Na⁺]_i using the Na⁺-sensitive probe, sodium-binding benzofuran isophthalate (SBFI). Hyperpolarization of spontaneously active dopamine neurons (recorded in current-clamp mode) caused the cessation of action potential firing accompanied by an elevation in Na⁺]_i. In dopamine neurons voltage-clamped at a holding potential of ?60 mV elevations of Na⁺]_i were induced by long-lasting (45–60 s) voltage jumps to more negative membrane potentials (–90 to ?120 mV) but not by corresponding voltage jumps to ?30 mV. These hyperpolarization-induced elevations of Na⁺]_i were depressed during inhibition of I_h, a hyperpolarization-activated inward current, by Cs⁺. Hyperpolarization-induced elevations in Na⁺]_i might occur also in other cell types which express a powerful I_h and might signal lack of postsynaptic activity.