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bioRxiv · 10.1101/2023.07.24.550111

M-type potassium currents differentially affect activation of motoneuron subtypes and tune recruitment gain

Sharples, S. A.·Broadhead, M. J.·Gray, J. A.·Miles, G. B.
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Abstract

The size principle is a key mechanism governing the orderly recruitment of motor units and is believed to be dependent on passive properties of the constituent motoneurons. However, motoneurons are endowed with voltage-sensitive ion channels that create non-linearities in their input-output functions. Here we describe a role for the M-type potassium current, conducted by KCNQ channels, in the control of motoneuron recruitment in mice. Motoneurons were studied with whole-cell patch clamp electrophysiology in transverse spinal slices and identified based on delayed (fast) and immediate (slow) onsets of repetitive firing. M-currents were larger in delayed compared to immediate firing motoneurons, which was not reflected by variations in the expression of Kv7.2 or Kv7.3 subunits. Instead, a more depolarized spike threshold in delayed-firing motoneurons afforded a greater proportion of the total M-current to become activated within the subthreshold voltage range, which translated to a greater influence on their recruitment with little influence on their firing rates. Pharmacological activation of M-currents also influenced motoneuron recruitment at the population level, producing a rightward shift in the recruitment curve of monosynaptic reflexes within isolated mouse spinal cords. These results demonstrate a prominent role for M-type potassium currents in regulating the function of motor units, which occurs primarily through the differential control of motoneuron subtype recruitment. More generally, these findings highlight the importance of active properties mediated by voltage-sensitive ion channels in the differential control of motoneuron recruitment, which is a key mechanism for the gradation of muscle force. Key PointsO_LIM-currents exert an inhibitory influence on spinal motor output. C_LIO_LIThis inhibitory influence is exerted by controlling the recruitment, but not the firing rate, of high-threshold fast-like motoneurons, with limited influence on low-threshold slow-like motoneurons. C_LIO_LIPreferential control of fast motoneurons may be linked to a larger M-current that is activated within the subthreshold voltage range compared to slow motoneurons. C_LIO_LILarger M-currents in fast compared to slow motoneurons are not accounted for by differences in Kv7.2 or Kv7.3 channel composition. C_LIO_LIThe orderly recruitment of motoneuron subtypes is shaped by differences in the contribution of voltage-gated ion channels, including KCNQ channels. C_LIO_LIKCNQ channels may provide a target to dynamically modulate the recruitment gain across the motor pool and readily adjust movement vigour. C_LI

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Sharples, S. A., Broadhead, M. J., Gray, J. A., Miles, G. B.. 2023-07-26. M-type potassium currents differentially affect activation of motoneuron subtypes and tune recruitment gain. https://doi.org/10.1101/2023.07.24.550111

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