Location, location, location: the organization and roles of potassium channels in mammalian motoneurons

Abstract

The spatial and temporal balance of spinal α‐motoneuron (αMN) intrinsic membrane conductances underlies the neural output of the final common pathway for motor commands. Although the complete set and precise localization of αMN K+ channels and their respective outward conductances remain unsettled, important K+ channel subtypes have now been documented, including Kv1, Kv2, Kv7, TASK, HCN and SK isoforms. Unique kinetics and gating parameters allow these channels to differentially shape and/or modify αMN firing properties, and recent immunohistochemical localization of K+‐channel complexes reveals a framework in which their spatial distribution and/or focal clustering within different surface membrane compartments is highly tuned to their physiological function. Moreover, highly evolved regulatory mechanisms enable specific channels to operate over variable levels of αMN activity and contribute to either state‐dependent enhancement or diminution of firing. While recent data suggest an additional, non‐conducting role for clustered Kv2.1 channels in the formation of endoplasmic reticulum–plasma membrane junctions postsynaptic to C‐bouton synapses, electrophysiological evidence demonstrates that conducting Kv2.1 channels effectively regulate αMN firing, especially during periods of high activity in which the cholinergic C‐boutons are engaged. Intense αMN activity or cell injury rapidly disrupts the clustered organization of Kv2.1 channels in αMNs and further impacts their physiological role. Thus, αMN K+ channels play a critical regulatory role in motor processing and are potential therapeutic targets for diseases affecting αMN excitability and motor output, including amyotrophic lateral sclerosis.

Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

“…The intrinsic excitability of neurons is influenced by their compartmental, geometric structures, which are endowed with specialized complements of ion channels that support flexible output ( Brocard, 2019 ; Deardorff et al, 2021 ; Heckman et al, 2008 ). For example, nonlinearities in the input-output relationship of motoneurons are produced by persistent inward currents (PICs) generated by persistent sodium and L-type calcium channels located on the axon initial segment (AIS) and distal dendrites, respectively ( Brocard et al, 2016 ; Chatelier et al, 2010 ; Hounsgaard et al, 1988 ; Hounsgaard and Kiehn, 1993 ; Lee and Heckman, 1998a ; Li and Bennett, 2003 ; Quinlan et al, 2011 ; Schwindt and Crill, 1980 ).…”

Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

“…The intrinsic excitability of neurons is influenced by their compartmental geometrical structures, which are endowed with specialized complements of ion channels that support flexible output [11][12][13] . For example, non-linearities in the input-output relationship of motoneurons are produced by persistent inward currents (PICs) generated by persistent sodium and L-type calcium channels located on the axon initial segment and distal dendrites respectively [14][15][16][17][18][19][20][21][22] .…”

“…The intrinsic excitability of neurons is influenced by their compartmental geometrical structures, which are endowed with specialized complements of ion channels that support flexible output (Brocard, 2019;Deardorff et al, 2021;Heckman et al, 2008a). For example, non-linearities in the input-output relationship of motoneurons are produced by persistent inward currents (PICs) generated by persistent sodium and L-type calcium channels located on the axon initial segment and distal dendrites respectively (Brocard et al, 2016;Chatelier et al, 2010;Hounsgaard et al, 1988;Hounsgaard and Kiehn, 1993;Lee and Heckman, 1998a;Li and Bennett, 2003;Quinlan et al, 2011;Crill, 1980, 1977).…”

Developmentally Regulated Modulation of Lumbar Motoneurons by Metabotropic Glutamate Receptors: A Cellular and Behavioral Analysis in Newborn Mice

“…To complete this analysis of the cellular basis of mGluR modulation in lumbar MNs, we examined the impact of the three mGluR agonists on the hyperpolarization-activated mixed cation current I H , another important cellular target of neuromodulatory systems in the spinal cord ( Deardorff et al, 2021 ). For this purpose, voltage steps of -60 mV from a holding membrane potential of -60 mV were applied and the instantaneous current evoked was measured immediately after the capacitive transient (filled diamond in Figure 5B1 ) and the steady-state current at the end of the hyperpolarizing pulse (open diamond in Figure 5B1 ) in control condition and in the presence of each mGluR agonist.…”