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.