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

Abstract

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. 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. 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. Sodium pump currents were 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). Strophanthidin currents were smaller in a reduced [K+]o (EC50= 0.2 mm). 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

Role of the Electrogenic Na/K Pump in Disinhibition-Induced Bursting in Cultured Spinal Networks

“…This current is directly proportional to the level of activity of the pump. Pump activity is known to be regulated by the spike rate in the network through the Na ϩ -loading of the cells (Shen and Johnson 1998). Therefore we wanted to know whether the depolarization induced by strophanthidin is dependent on the overall network activity.…”

“…The difference in membrane potential between the basic level and the "dynamic" level of pump activity was similar to the amount of hyperpolarization induced by disinhibition. This suggests that during disinhibition the supplementary Na ϩ influx during the bursts accelerates the pump turnover (Shen and Johnson 1998) and this higher level of activity of the pump during the burst is responsible for the hyperpolarization of the membrane potential after the bursts (postburst AHP). In line with this hypothesis, the upregulation of the pump could be mimicked in single cells in the absence of network activity by mimicking bursts by current injection (see Fig.…”

“…On the other hand, the decrease in the pump activity at hyperpolarized potential may play a significant role in stabilizing the membrane potential. Shen and Johnson (1998) assumed that the ability to generate pump currents at high density may be a necessary condition for enabling burst firing during NMDA-induced bursting in rat midbrain dopamine neurons.…”

“…Furthermore, pump currents are involved in rhythm generation in invertebrates (Tsai and Chen 1995), brain stem motoneurons (Del Negro et al 1999), and dopaminergic neurons (Shen and Johnson 1998). In the isolated spinal cord, the role of the pump in spinal interneurons could only be assumed because there was no direct experimental access to these neurons.…”

Inhibitory Effects of Clofilium on Membrane Currents Associated with Ca²⁺ Channels, NMDA Receptor Channels and Na⁺, K⁺-ATPase in Cortical Neurons

“…The tonic activity of the Na + , K + -ATPase can be revealed by an ouabain-and strophanthidin-sensitive inward current recorded by whole-cell recording in heart cells and neurons [32][33][34]. Consistent with previous demonstrations [33,34], the ouabain-and strophanthidin-induced current in cortical neurons was sensitive to changes in extracellular Na + , intracellular K + , and cellular ATP level [32]. When added to the extracellular solution, clofilium inhibited the Na + pump current at -60 mV in a concentrationdependent manner, with an IC 50 of 7.5 Ìmol/l (fig.…”