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

• DOI: 10.7554/elife.54916
• Publication Date: 2020-11-09T13:01:26Z
• Authors: Shawn M Lamothe; Nazlee Sharmin; Grace Silver; Motoyasu Satou; Yubin Hao; Toru Tateno; Victoria A Baronas; Harley T Kurata
• Keywords: 0301 basic medicine; QH301-705.5; Science; 7. Clean energy; Cell Line; Large Neutral Amino Acid-Transporter 1; Mice; 03 medical and health sciences; voltage-dependent gating; Animals; Humans; Biology (General); 2. Zero hunger; 0303 health sciences; Kv1.2; Kv1.1; Q; R; Fibroblasts; 3. Good health; Electrophysiology; Slc7a5; Gene Expression Regulation; Gene Knockdown Techniques; Medicine; Kv1.1 Potassium Channel; Ion Channel Gating; potassium channel; Neuroscience

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 voltage-sensing domain controls the sensitivity and response to Slc7a5, and localize a specific position in S1 with prominent effects on Slc7a5 sensitivity. Overall, our study highlights multiple Slc7a5-sensitive Kv1 subunits, and identifies the voltage-sensing domain as a determinant of Slc7a5 modulation of Kv1 channels.