Redistribution of Kv2.1 ion channels on spinal motoneurons following peripheral nerve injury

• Published in: Brain research Vol. 1547; pp. 1 - 15
• Main Authors: Romer, Shannon H, Dominguez, Kathleen M, Gelpi, Marc W, Deardorff, Adam S, Tracy, Robert C, Fyffe, Robert. E.W
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 14.02.2014; Elsevier
• Subjects: Animals; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Kv2.1; Motoneuron; Motor Neurons - metabolism; Neurology; Peripheral Nerve Injuries - metabolism; Peripheral nerve injury; Rats; Rats, Sprague-Dawley; Shab Potassium Channels - metabolism; Tibial Nerve - injuries; Tibial Nerve - metabolism; Vertebrates: nervous system and sense organs; Voltage-gated ion channels; immunoreactivity; MN; lateral gastrocnemius muscle; Voltage-gated ion channels; IR; PNI; peripheral Nerve Injury; medial gastrocnemius muscle; CTB; motoneuron; MG; LG; Kv2.1; cholera toxin subunit B; Peripheral nerve injury; Motoneuron; Peripheral nerve; Ionic channel; Motor neuron; Lesion
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2013.12.012

Abstract Pathophysiological responses to peripheral nerve injury include alterations in the activity, intrinsic membrane properties and excitability of spinal neurons. The intrinsic excitability of α-motoneurons is controlled in part by the expression, regulation, and distribution of membrane-bound ion channels. Ion channels, such as Kv2.1 and SK, which underlie delayed rectifier potassium currents and afterhyperpolarization respectively, are localized in high-density clusters at specific postsynaptic sites ( Deardorff et al., 2013; Muennich and Fyffe, 2004 ). Previous work has indicated that Kv2.1 channel clustering and kinetics are regulated by a variety of stimuli including ischemia, hypoxia, neuromodulator action and increased activity. Regulation occurs via channel dephosphorylation leading to both declustering and alterations in channel kinetics, thus normalizing activity ( Misonou et al., 2004; Misonou et al., 2005; Misonou et al., 2008; Mohapatra et al., 2009; Park et al., 2006 ). Here we demonstrate using immunohistochemistry that peripheral nerve injury is also sufficient to alter the surface distribution of Kv2.1 channels on motoneurons. The dynamic changes in channel localization include a rapid progressive decline in cluster size, beginning immediately after axotomy, and reaching maximum within one week. With reinnervation, the organization and size of Kv2.1 clusters do not fully recover. However, in the absence of reinnervation Kv2.1 cluster sizes fully recover. Moreover, unilateral peripheral nerve injury evokes parallel, but smaller effects bilaterally. These results suggest that homeostatic regulation of motoneuron Kv2.1 membrane distribution after axon injury is largely independent of axon reinnervation.