title: The Role of Kv1.2 Channel in Electrotaxis Cell Migration.
abstract: Voltage-gated potassium Kv1.2 channels play pivotal role in maintaining of resting membrane potential and, consequently, regulation of cellular excitability of neurons. Endogenously generated electric field (EF) have been proven as an important regulator for cell migration and tissue repair. The mechanisms of ion channel involvement in EF-induced cell responses are extensively studied but largely are poorly understood. In this study we generated three COS-7 clones with different expression levels of Kv1.2 channel, and confirmed their functional variations with patch clamp analysis. Time-lapse imaging analysis showed that EF-induced cell migration response was Kv1.2 channel expression level depended. Inhibition of Kv1.2 channels with charybdotoxin (ChTX) constrained the sensitivity of COS-7 cells to EF stimulation more than their motility. Immunocytochemistry and pull-down analyses demonstrated association of Kv1.2 channels with actin-binding protein cortactin and its re-localization to the cathode-facing membrane at EF stimulation, which confirms the mechanism of EF-induced directional migration. This study displays that Kv1.2 channels represent an important physiological link in EF-induced cell migration. The described mechanism suggests a potential application of EF which may improve therapeutic performance in curing injuries of neuronal and/or cardiac tissue repair, post operational therapy, and various degenerative syndromes.
authors.affiliation: Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, China.|School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Mathew
authors.initials: M
authors.lastname: Edmundson
authors.affiliation: School of Biosciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Telezhkin
authors.affiliation: School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gu
authors.affiliation: School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wei
authors.affiliation: School of Biosciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kemp
authors.affiliation: Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, China.|School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Bing
authors.initials: B
authors.lastname: Song
mesh_terms: D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000187:drug effects; D002522:Chlorocebus aethiops; D051356:Cortactin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D047468:Immunoprecipitation; D051662:Kv1.1 Potassium Channel / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011485:Protein Binding; D015398:Signal Transduction; D013997:Time Factors; D059008:Time-Lapse Imaging; D014162:Transfection
chemical_list: D051356:Cortactin; C496947:Kcna1 protein, mouse; D026902:Potassium Channel Blockers; D051662:Kv1.1 Potassium Channel