Dynamic Redistribution of Kv2.1 Ion Channels on Spinal Motoneurons Following Increased Neural Activity

Abstract

<p>Pathophysiological conditions such as peripheral nerve Injury cause significant alterations in neuronal activity and excitability as well as changes in synaptic organization in spinal motor circuits. However, despite successful reinnervation of peripheral targets after injury, seldom the recovery of motor function is complete. The intrinsic excitability of motoneurons is controlled in part by the expression of voltage gated ion channels. Kv2.1 channels, which underlie delayed rectifier potassium currents, are localized in high density macroclusters (>1μm2) and miniclusters (1 μm2) on the soma and proximal dendrites at specific postsynaptic sites in spinal motoneurons (Muennich and Fyffe, 2003). Kv2.1 channel properties and membrane clustering are phosphorylation dependent (e.g. Park et aI., 2006) and highly regulated by a variety of stimuli including ischemia, hypoxia, neuromodulator action and activity. Increased neuronal activity dephosphorylates Kv2.1 through Calcium-Calcineurin dependent mechanisms leading to declustering and a hyperpolarizing shift in activation of the delayed rectifier current (Misonou et ai, 2004). Following peripheral nerve inJury, Kv2.1 macroclusters decrease in both number and cluster area in spinal motoneurons. Therefore, we hypothesize that the Kv2.1 clustering might be modulated by the changes in activity following peripheral nerve injury. To test this hypothesis we analyzed with confocal microscopy the surface distribution of Kv2.1 channels revealed by immunohistochemistry. The results indicate a decrease in size and number of Kv2.1 macroclusters following in vivo nerve stimulation and in vitro stimulation with glutamate and muscarine. These data suggest that an increase in motoneuron activity can cause a redistribution of Kv2.1-IR similar to the Kv2.1-IR seen following peripheral nerve injury. The dynamic regulation of Kv2.1 channels after peripheral nerve injury may be related to changes in motoneuron excitability.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>