Co-expression of Kv1.5 with Kvβ1.2 in HEK293 cells resulted in significant membrane hyperpolarization following acute H2O2 exposure, confirming the redox sensitivity of Kvβ1.2.
The Kvβ1.2 subunit enhances the redox sensitivity of Kv1.5 channels, causing membrane hyperpolarization under oxidative stress, highlighting its potential as a therapeutic target.
Voltage-gated potassium (Kv) channels help regulate membrane potential and processes likecell proliferation. Among these, Kv1.5 is known to respond to redox changes. Our lab's previouswork has demonstrated that the Kvβ1.2 subunit inhibits proliferation when co-expressed withKv1.5 in HEK293 cells. On the basis of these findings, we hypothesized that Kvβ1.2 alsoenhances redox sensitivity by causing hyperpolarization of the membrane under oxidativestress.To determine this, we used cells expressing Kv1.5 channel only, cells co-expressing Kv1.5 withKvβ1.2 subunit, or HEK293 cells with no channel expression as an additional control. All groupswere treated with 60mM of KCl (positive control, expected to produce robust depolarization in allcells), DPO (Kv1.5 blocker, expected to produce depolarization in Kv1.5 + Kvβ1.2 cells), H 2 O 2 (free radical, expected to produce hyperpolarization in Kv1.5 + Kvβ1.2 cells), along with H 2 O 2 +DPO and dye only conditions for additional intermediate measurements. After FLIPR dyeloading, we assessed membrane potential changes by using corrected fluorescence intensity(cell – background) fluorescence from 3–6 images, with six cells analyzed per image inreplicate experiments.Cells expressing Kv1.5 + Kvβ1.2 showed significantly reduced fluorescence following acute H 2 O 2 treatment consistent with membrane hyperpolarization. Both DPO and KCl had significantincreases in fluorescence, consistent with depolarization. On the other hand, Kv1.5-onlyexpressing cells exhibited negligible fluorescence changes across conditions, signifying thatthey are not redox sensitive.In conclusion, cells expressing Kv1.5+ Kvβ1.2 hyperpolarized in response to acute H 2 O 2 exposure, confirming the redox sensitivity of Kvβ1.2. We have not observed hyperpolarization inresponse to H 2 O 2 in cells expressing Kv1.5 only or in HEK293 cells with no channel expression. Our findings highlight involvement of Kvβ1.2 in regulating membrane potential, advancing itsrole as a potential therapeutic target in pathologic conditions such as cardiovascular diseaseand tumorogenesis. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Molitor et al. (Fri,) reported a other. H2O2, DPO, KCl vs. Kv1.5-only expressing cells or no channel expression was evaluated on Membrane potential changes assessed by corrected fluorescence intensity. Co-expression of Kv1.5 with Kvβ1.2 in HEK293 cells resulted in significant membrane hyperpolarization following acute H2O2 exposure, confirming the redox sensitivity of Kvβ1.2.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: