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. 2017 May 18;7:2075. doi: 10.1038/s41598-017-02129-w

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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The relationship between HIF-1α and Kv3.4 (A) Out of eight oxygen-sensitive Kv channels (Kv1.2, Kv1.3, Kv1.4, Kv2.1, Kv3.1, Kv3.3, Kv3.4, and Kv9.3), only Kv3.4 from among eight was significantly up-regulated by transient HIF-1α siRNA transfection. (B) PX-478 (40 µM), a HIF-1α-specific blocker, inhibited HIF-1α and up-regulated Kv3.4 mRNA expression. (C) HIF-1α accumulated upon 100 µM CoCl₂ treatment, and CoCl₂-induced HIF-1α accumulation was inhibited by 40 µM PX-478 treatment: 4 h of PX-478 pretreatment followed by 6 h of CoCl₂ and PX-478 treatment. (D) Kv3.4 mRNA expression was down-regulated after 4 h of 100 µM CoCl₂ treatment. PX-478 pretreatment recovered the down-regulation of Kv3.4 mRNA expression induced by CoCl₂. (E) Kv3.4 (70 kDa) was decreased after 6 h of CoCl₂ treatment. The decrease in Kv3.4 (70 kDa) expression was recovered by PX-478 pretreatment (4 h) followed by 6 h of CoCl₂ and PX-478 treatment. (F) Currents sensitive to BDS-II (100 nM) were detected at +30 and +40 mV of depolarization (n = 6), whereas BDS-II-sensitive currents were diminished by 100 µM CoCl₂ treatment (n = 6). Diminished BDS-II-sensitive currents were recovered by 40 µM PX-478 pretreatment at +20, +30, and +40 mV of depolarization (n = 9). Experiments were repeated in triplicate or the indicated times, and data represent the mean ± standard error. *, ^#p < 0.05 and **p < 0.01 versus the control value.