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Novel potassium channel blocker, 4-AP-3-MeOH, inhibits fast potassium channels and restores axonal conduction in injured guinea pig spinal cord white matter

We have demonstrated that 4-aminopyridine-3-methanol (4-AP-3-MeOH), a 4-aminopyridine derivative, significantly restores axonal conduction in stretched spinal cord white-matter strips and shows no preference in restoring large and small axons. This compound is 10 times more potent when compared with 4-AP and other derivatives in restoring axonal conduction. Unlike 4-AP, 4-AP-3-MeOH can restore axonal conduction without changing axonal electrophysiological properties. In addition, we also have confirmed that 4-AP-3-MeOH is indeed an effective blocker of I(A) based on patch-clamp studies using guinea pig dorsal root ganglia cells. Furthermore, we have also provided the critical evidence to confirm the unmasking of potassium channels following mechanical injury. Taken together, our data further supports and implicates the role of potassium channels in conduction loss and its therapeutic value as an effective target for intervention to restore function in spinal cord trauma. Furthermore, due to its high potency and possible low side effect of impacting electrophysiological properties, 4-AP-3-MeOH is perhaps the optimal choice in reversing conduction block in spinal cord injury compared with other derivatives previously reported from this group

Keywords : Aminopyridines,Animals,antagonists & inhibitors,Axons,Cells,Cultured,chemistry,drug effects,drug therapy,Female,Ganglia,Spinal,Guinea Pigs,In Vitro Techniques,injuries,Kv1.2 Potassium Channel,Membrane Potentials,metabolism,Nerve Fibers,Myelinated,Neural Conduction,Neurons,Neuroprotective Agents,Patch-Clamp Techniques,pharmacology,physiology,physiopathology,Potassium Channel Blockers,Spinal Cord,Spinal Cord Injuries,Time,, Potassium,Channel,Blocker,4ap3meoh,Inhibits, stress and chronic pain

Date of Publication : 2010 Jan

Authors : Sun W;Smith D;Fu Y;Cheng JX;Bryn S;Borgens R;Shi R;

Organisation : Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA

Journal of Publication : J Neurophysiol

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/19923250

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