title: Rearrangement of potassium ions and Kv1.1/Kv1.2 potassium channels in regenerating axons following end-to-end neurorrhaphy: ionic images from TOF-SIMS.
abstract: The voltage-gated potassium channels Kv1.1 and Kv1.2 that cluster at juxtaparanodal (JXP) regions are essential in the regulation of nerve excitability and play a critical role in axonal conduction. When demyelination occurs, Kv1.1/Kv1.2 activity increases, suppressing the membrane potential nearly to the equilibrium potential of K+, which results in an axonal conduction blockade. The recovery of K+-dependent communication signals and proper clustering of Kv1.1/Kv1.2 channels at JXP regions may directly reflect nerve regeneration following peripheral nerve injury. However, little is known about potassium channel expression and its relationship with the dynamic potassium ion distribution at the node of Ranvier during the regenerative process of peripheral nerve injury (PNI). In the present study, end-to-end neurorrhaphy (EEN) was performed using an in vivo model of PNI. The distribution of K+at regenerating axons following EEN was detected by time-of-flight secondary-ion mass spectrometry. The specific localization and expression of Kv1.1/Kv1.2 channels were examined by confocal microscopy and western blotting. Our data showed that the re-establishment of K+distribution and intensity was correlated with the functional recovery of compound muscle action potential morphology in EEN rats. Furthermore, the re-clustering of Kv1.1/1.2 channels 1 and 3 months after EEN at the nodal region of the regenerating nerve corresponded to changes in the K+distribution. This study provided direct evidence of K+distribution in regenerating axons for the first time. We proposed that the Kv1.1/Kv1.2 channels re-clustered at the JXP regions of regenerating axons are essential for modulating the proper patterns of K+distribution in axons for maintaining membrane potential stability after EEN.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung, 40201, Taiwan.|Department of Medical Education, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd, Taichung, Taiwan.
authors.forename: Chiung-Hui
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung, 40201, Taiwan.
authors.forename: Tsung-Huan
authors.initials: TH
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung, 40201, Taiwan.
authors.forename: Li-You
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung, 40201, Taiwan.
authors.forename: Yin-Shuo
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung, 40201, Taiwan.
authors.forename: To-Jung
authors.initials: TJ
authors.lastname: Tseng
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung, 40201, Taiwan. khrnangel@gmail.com.|Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. khrnangel@gmail.com.
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Liao
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D007477:Ions / Q000378:metabolism; D051662:Kv1.1 Potassium Channel / Q000378:metabolism*; D051663:Kv1.2 Potassium Channel / Q000378:metabolism*; D008297:Male; D009411:Nerve Endings / Q000378:metabolism* / Q000473:pathology; D009416:Nerve Regeneration; D019635:Neurosurgical Procedures; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018629:Spectrometry, Mass, Secondary Ion; D013997:Time Factors
chemical_list: D007477:Ions; D051663:Kv1.2 Potassium Channel; D051662:Kv1.1 Potassium Channel; D011188:Potassium
keywords: End-to-end neurorrhaphy (EEN); Juxtaparanodal region; Kv1.1; Kv1.2; Voltage-gated potassium channels (Kv channels)