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bioRxiv · 10.1101/2020.01.17.910059

Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels

Sharmin, N.·Lamothe, S. M.·Baronas, V. A.·Silver, G.·Hao, Y.·Kurata, H. T.
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Abstract

Many voltage-dependent ion channels are regulated by accessory proteins, although the underlying mechanisms and consequences are often poorly understood. We recently reported a novel function of the amino acid transporter Slc7a5 as a powerful regulator of Kv1.2 voltage-dependent activation. 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. Disinhibition of Kv1.1 is strongly attenuated by shRNA knockdown of endogenous Slc7a5. We investigated a variety of chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltage-sensing domain controls the sensitivity and response to Slc7a5. Overall, our study highlights additional Slc7a5-sensitive Kv1 subunits, and demonstrates that features of Slc7a5 sensitivity can be swapped by exchanging voltage-sensing domains. IMPACT STATEMENTThe voltage-sensing mechanism of a subfamily of potassium channels can be powerfully modulated in unconventional ways, by poorly understood regulatory partners.

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Sharmin, N., Lamothe, S. M., Baronas, V. A., Silver, G., Hao, Y., Kurata, H. T.. 2020-01-17. Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels. https://doi.org/10.1101/2020.01.17.910059

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