biostudies-literatureLamothe SMNatural Sciences and Engineering Research Council of CanadaAlberta Diabetes InstituteUniversity of AlbertaCanadian Institutes of Health ResearchCIHRe54916https://www.ebi.ac.uk/biostudies/studies/S-EPMC7690953biostudies-literatureUnknown9Many voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium channels by the amino acid transporter Slc7a5. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement ('disinhibition') with holding potentials more negative than -120 mV. Knockdown of endogenous Slc7a5 leads to larger Kv1.1 currents and strongly attenuates the disinhibition effect, suggesting that Slc7a5 regulation of Kv1.1 involves channel inhibition that can be reversed by supraphysiological hyperpolarizing voltages. We investigated chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltageLifeControl of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels.PMC7690953Early Career InvestigatorRowland and Muriel Haryett fellowshipSalary supportUSRAProject GrantVanier StudentshipBaronas VATateno TKurata HTLamothe SMSharmin NSatou MHao YSilver GfalseControl of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels.Many voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium channels by the amino acid transporter Slc7a5. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement ('disinhibition') with holding potentials more negative than -120 mV. Knockdown of endogenous Slc7a5 leads to larger Kv1.1 currents and strongly attenuates the disinhibition effect, suggesting that Slc7a5 regulation of Kv1.1 involves channel inhibition that can be reversed by supraphysiological hyperpolarizing voltages. We investigated chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltag2020-01-01T00:00:00Z2020 Nov2026-05-02T11:23:22.026Z2025-02-19T03:26:50.477ZS-EPMC76909533316474610.7554/eLife.54916