Sodium pump regulation of locomotor control circuits

Abstract

Sodium pumps are ubiquitously expressed membrane proteins that extrude three Na ions in exchange for two K ions, using ATP as an energy source. Recent studies have illuminated additional, dynamic roles for sodium pumps in regulating the excitability of neuronal networks in an activity-dependent fashion. We review their role in a novel form of short-term memory within rhythmic locomotor networks. The data we review derives mainly from recent studies on tadpoles and neonatal mice. The role and underlying mechanisms of pump action broadly match previously published data from an invertebrate, the larva. We therefore propose a highly conserved mechanism by which sodium pump activity increases following a bout of locomotion. This results in an ultraslow afterhyperpolarization (usAHP) of the membrane potential that lasts around 1 min, but which only occurs in around half the network neurons. This usAHP in turn alters network excitability so that network output is reduced in a locomotor interval-dependent manner. The pumps therefore confer on spinal locomotor networks a temporary memory trace of recent network performance.

The M-current works in tandem with the persistent sodium current to set the speed of locomotion

“…Among general principles of rhythmogenesis, outward conductances are required to repolarize bursts [15]. In vertebrates, the Ca 2+ -activated K + current (I KCa ) appears important in repolarizing bursts to regulate the locomotor rhythm [16][17][18][19], among other hyperpolarizing currents mediated by Kv1.2 [20] and A-type K + channels [21] or Na + /K + pumps [22][23][24]. Considering I NaP as a subthreshold persistent conductance critically engaged in the burst initiation, it might be efficiently counteracted by a subthreshold persistent potassium current to end bursts of pacemakers and thereby to regulate the locomotor cycle.…”

Neural interactions in developing rhythmogenic spinal networks: Insights from computational modeling

“…At the same time, we know that spinal neurons, and particularly Shox2 neuron types contain other ionic channels, including T-type calcium and h currents and different Ca 2+ and Ca 2+ -dependent potassium currents that can also support pacemaker properties and have been implicated in locomotor-like activity (Wilson et al, 2005; Anderson et al, 2012; Kiehn, 2016; Brocard, 2019). In addition, there is indirect evidence of an important role of Na + /K + pump in CPG operation (Kueh et al, 2016) and particularly in the neonatal spinal cords of mice (Picton et al, 2017). The role of Na + /K + pump current has been previously included in the computational models of Hb9 neurons (Brocard et al, 2013) and can be included in Shox2 neuron models in the future.…”

Neural Interactions in Developing Rhythmogenic Spinal Networks: Insights From Computational Modeling

“…At the same time, we know that spinal neurons contain other ionic channels, including T-type calcium and h currents and different Ca 2+ and Ca 2+ -dependent potassium currents that can also support pacemaker properties and have been implicated in locomotor-like activity (Wilson et al, 2005 ; Anderson et al, 2012 ; Kiehn, 2016 ; Brocard, 2019 ). In addition, there is indirect evidence of an important role of Na + /K + pump in CPG operation (Kueh et al, 2016 ) and particularly in the neonatal spinal cords of mice (Picton et al, 2017 ). The Na + /K + pump current has been previously included in the computational models of Hb9 neurons (Brocard et al, 2013 ) and can be included in Shox2 neuron models in the future.…”