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- W4319916028 abstract "Voltage-gated potassium channels (VGKCs) play fundamental roles in neurobiology; they are a major hub for potential modulation of cell excitability and health. VGKCs are formed by homotetramerization of K+ channels subunits (Kv1-12). Kv2 channels are the major cause of the delayed rectifying K+ currents (IKdr) that tune neuronal firing frequency. Uniquely, Kv2 subunits can co-assemble with members of four other families of Kv (Kv5-6, 8-9). These other Kvs are named silent since they do not form functional channels themselves as homomeric VGKCs. Heteromeric co-assemblies (hetVGKCs) form biophysically distinct channels that modify IKdr and therefore determine neuronal excitability. More than that, the expression of silent subunits suppresses the overall expression of Kv2 subunits, affecting the abundancy of homomeric Kv2 channels and heteromeric channels containing Kv2 subunits. To date, no established mechanism explains how silent Kv subunits interfere with hetVGKCs gating processes or how the mechanism of suppression works. Here, we used Kv6.4 as archetypal silent subunit expressed together with Kv2.1 in HEK cells. Keeping the total amount of Kv2.1 plasmid constant, we found a significant decrease in the magnitude of currents with increasing Kv6.4 dose (ANOVA, p<0.05). To more cleanly assess biophysical differences between homo- and heterotetramers, we generated a Kv2.1-Kv6.4 dimer and compared currents recorded from cells transfected with Kv2.1 plasmid only vs those transfected with dimer plasmid only. We found a significant hyperpolarizing shift in inactivation V50 (−79.6 mV vs −53.5 mV, t-test, p=0.0001), significantly larger activation slope (20.7 vs 14.9, t-test, p=0.0014) and faster activation kinetics (2-way ANOVA, p=0.0354) for the dimer currents compared to Kv2.1-only currents. These results highlight several ways in which silent subunits modify the function of Kv2.1 currents." @default.
- W4319916028 created "2023-02-11" @default.
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- W4319916028 date "2023-02-01" @default.
- W4319916028 modified "2023-09-30" @default.
- W4319916028 title "Modulation of delayed rectifying K+ currents by silent Kv subunits" @default.
- W4319916028 doi "https://doi.org/10.1016/j.bpj.2022.11.2110" @default.
- W4319916028 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36783954" @default.
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