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

Abstract

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.