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These abnormalities were studied by mathematical modeling in human regenerated nerves and experimental studies in mice. In three adult male patients with surgically repaired complete injuries of peripheral nerves of the arm 22\u00a0months\u201326\u00a0years <jats:italic>prior to<\/jats:italic> investigation, deviation of excitability measures was explained by a hyperpolarizing shift in the resting membrane potential and an increase in the passive \u2018Barrett and Barrett\u2019 conductance (<jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>) bridging the nodal and internodal compartments. These changes were associated with an increase in the \u2018fast\u2019 K<jats:sup>+<\/jats:sup> conductance and the inward rectifier conductance (<jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>). Similar changes were found in regenerated mouse tibial motor axons at 1\u00a0month after a sciatic crush lesion. During the first 5\u00a0months of regeneration, <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> showed partial recovery, which paralleled that in <jats:styled-content style=\"fixed-case\">GBB<\/jats:styled-content>. The internodal length remained one\u2010third of normal. Excitability abnormalities could be reversed by the energy\u2010dependent Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> pump blocker ouabain resulting in membrane depolarization. Stressing the Na<jats:sup>+<\/jats:sup> pumping system during a strenuous activity protocol triggered partial Wallerian degeneration in regenerated nerves but not in control nerves from age\u2010matched mice. The current data suggest that the nodal voltage\u2010gated ion channel machinery is restored in regenerated axons, although the electrical separation from the internodal compartment remains compromised. Due to the persistent increase in number of nodes, the increased activity\u2010dependent Na<jats:sup>+<\/jats:sup> influx could lead to hyperactivity of the Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> pump resulting in membrane hyperpolarization and neurotoxic energy insufficiency during strenuous activity.<\/jats:p>","DOI":"10.1111\/ejn.13047","type":"journal-article","created":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T08:31:24Z","timestamp":1439973084000},"page":"388-403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Persistent alterations in active and passive electrical membrane properties of regenerated nerve fibers of man and mice"],"prefix":"10.1111","volume":"43","author":[{"given":"Mihai","family":"Moldovan","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Pharmacology University of Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Neurophysiology NF3063 Rigshospitalet 9 Blegdamsvej 2100 Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology University of Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Neurophysiology NF3063 Rigshospitalet 9 Blegdamsvej 2100 Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette R.","family":"Rosberg","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology University of Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Neurophysiology NF3063 Rigshospitalet 9 Blegdamsvej 2100 Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Krarup","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology University of Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Neurophysiology NF3063 Rigshospitalet 9 Blegdamsvej 2100 Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,10,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-07-02602.2000"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.03.022"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.03.017"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.02.006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2013.04.012"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.08.041"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.05.034"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016395"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1982.sp014064"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.03.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1152\/jn.1944.7.2.103","article-title":"The electrical activity of regenerating nerves in the cat","volume":"7","author":"Berry C.M.","year":"1944","journal-title":"J. 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