Sodium pump evokes high density pump currents in rat midbrain dopamine neurons

1. Patch pipettes contained various concentrations of Na⁺ ([Na⁺](pip)) in order to record strophanthidin-sensitive currents under voltage clamp in dopamine neurons in slices of rat substantia nigra and ventral tegmental area. 2. When [Na⁺](pip) was 40 mM and the external K⁺ concentration ([K⁺](o)) was 2.5 mM, strophanthidin (10 μM) evoked 461 ± 121 pA of inward current. This effect was concentration dependent, with an EC₅₀ of 7.1 ± 2.6 μM. At potentials of -60 to -120 mV, strophanthidin-induced currents were not associated with significant changes in chord conductance. 3. Strophanthidin (10 μM) evoked 234 ± 43 pA of inward current when [Na⁺](pip) was 0.6 mM, and 513 ± 77 pA when [Na⁺](pip) was 80 mM. Despite higher pump currents with greater [Na⁺](pip), the strophanthidin EC₅₀ was not significantly different for any of six different [Na⁺](pip). 4. Sodium pump currents mere half-maximal when the [Na⁺](pip) was about 1.3 mM. Maximum pump current was estimated at 830 pA (29 μA cm^-2) at concentrations of intracellular Na⁺ that were assumed to be saturating (50-100 mM). 5. Strophanthidin currents were smaller in a reduced [K⁺](o) (EC₅₀ = 0.2 mM). 6. These data show that intracellular Na⁺ loading evokes relatively large pump currents. Our results are consistent with the physiological role of the sodium pump in burst firing in midbrain dopamine neurons.