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

摘要

The spatial and temporal balance of spinal alpha-motoneuron (alpha MN) intrinsic membrane conductances underlies the neural output of the final common pathway for motor commands. Although the complete set and precise localization of alpha MN 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 alpha MN 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 alpha MN 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 alpha MN firing, especially during periods of high activity in which the cholinergic C-boutons are engaged. Intense alpha MN activity or cell injury rapidly disrupts the clustered organization of Kv2.1 channels in alpha MNs and further impacts their physiological role. Thus, alpha MN K+ channels play a critical regulatory role in motor processing and are potential therapeutic targets for diseases affecting alpha MN excitability and motor output, including amyotrophic lateral sclerosis.