Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels
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
DOI:
10.7554/elife.54916
Publication Date:
2020-11-09T13:01:26Z
AUTHORS (8)
ABSTRACT
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.
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CITATIONS (8)
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