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

Journal of Neurophysiology
Wenjing SunRiyi Shi

Abstract

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 fro...Continue Reading

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Citations

Oct 13, 2011·Journal of Neurotrauma·Wenjing SunRiyi Shi
Jun 20, 2013·Neural Computation·Vladislav Volman, Laurel J Ng
Oct 12, 2013·International Journal of Molecular Sciences·Melissa Tully, Riyi Shi
Jul 6, 2014·Journal of Computational Neuroscience·Vladislav Volman, Laurel J Ng
Jul 21, 2012·Steroids·Kari V AhonenErkki T Kolehmainen
Mar 12, 2011·Journal of Neuroscience Research·Wang-Mi LiuQi-Xin Chen
Aug 9, 2011·Molecular Nutrition & Food Research·Riyi ShiWenjing Sun
Mar 4, 2015·Glia·Florentia Papastefanaki, Rebecca Matsas
May 11, 2016·Experimental Neurology·Andrea TedeschiMichael Costigan
Sep 22, 2016·Neural Regeneration Research·Jessica C Page, Riyi Shi
Sep 9, 2017·Neuroscience Bulletin·Xiaoyan ChenJunxia Xie
Jul 26, 2018·Annual Review of Cell and Developmental Biology·Michele Curcio, Frank Bradke
May 17, 2014·Expert Review of Neurotherapeutics·Melissa TullyRiyi Shi
Aug 5, 2017·Medical & Biological Engineering & Computing·Ehsan Daneshi KohanCarolyn Jennifer Sparrey
Nov 20, 2015·Journal of Neurophysiology·Rui YanRiyi Shi
Feb 6, 2020·Dose-response : a Publication of International Hormesis Society·Yan ChenDanmou Xin
Nov 22, 2018·Topics in Spinal Cord Injury Rehabilitation·Joshua WienerRobert Teasell
Jan 11, 2020·Scientific Reports·Sofia Rodríguez-RangelJorge E Sánchez-Rodríguez

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