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However, a limited number of studies have examined the effect of hypoxia in combination with inflammation (Hypo-Inf) on neural function. We previously reported that neuronal excitability in hippocampal CA1 neurons decreased during hypoxia and greatly rebounded upon reoxygenation. We attributed this altered excitability mainly to the dynamic regulation of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels and input resistance. However, the molecular mechanisms underlying input resistance changes by Hypo-Inf and reperfusion remained unclear. In the present study, we found that a change in the density of the delayed rectifier potassium current (I<jats:sub>DR<\/jats:sub>) can explain the input resistance variability. Furthermore, voltage-dependent inactivation of A-type potassium (I<jats:sub>A<\/jats:sub>) channels shifted in the depolarizing direction during Hypo-Inf and reverted to normal upon reperfusion without a significant alteration in the maximum current density. Our results indicate that changes in the input resistance, and consequently excitability, caused by Hypo-Inf and reperfusion are at least partially regulated by the availability and voltage dependence of K<jats:sub>V<\/jats:sub> channels. Moreover, these results suggest that selective K<jats:sub>V<\/jats:sub> channel modulators can be used as potential neuroprotective drugs to minimize hypoxia- and reperfusion-induced neuronal damage.<\/jats:p>","DOI":"10.1186\/s13041-021-00857-9","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T21:04:21Z","timestamp":1632431061000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hypoxia with inflammation and reperfusion alters membrane resistance by dynamically regulating voltage-gated potassium channels in hippocampal CA1 neurons"],"prefix":"10.1186","volume":"14","author":[{"given":"Yoon-Sil","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Ho","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3780-0522","authenticated-orcid":false,"given":"Jong-Cheol","family":"Rah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"857_CR1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/jcbfm.2009.189","volume":"30","author":"X Zhan","year":"2010","unstructured":"Zhan X, Ander BP, Jickling G, Turner R, Stamova B, Xu H, et al. 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