151. Subtype-specific responses of hKv7.4 and hKv7.5 channels to polyunsaturated fatty acids reveal an unconventional modulatory site and mechanism.
- Author
-
Frampton DJA, Choudhury K, Nikesjö J, Delemotte L, and Liin SI
- Subjects
- Fatty Acids, Unsaturated pharmacology, Potassium Channels, Voltage-Gated physiology
- Abstract
The K
V 7.4 and KV 7.5 subtypes of voltage-gated potassium channels play a role in important physiological processes such as sound amplification in the cochlea and adjusting vascular smooth muscle tone. Therefore, the mechanisms that regulate KV 7.4 and KV 7.5 channel function are of interest. Here, we study the effect of polyunsaturated fatty acids (PUFAs) on human KV 7.4 and KV 7.5 channels expressed in Xenopus oocytes. We report that PUFAs facilitate activation of hKV 7.5 by shifting the V50 of the conductance versus voltage (G(V)) curve toward more negative voltages. This response depends on the head group charge, as an uncharged PUFA analogue has no effect and a positively charged PUFA analogue induces positive V50 shifts. In contrast, PUFAs inhibit activation of hKV 7.4 by shifting V50 toward more positive voltages. No effect on V50 of hKV 7.4 is observed by an uncharged or a positively charged PUFA analogue. Thus, the hKV 7.5 channel's response to PUFAs is analogous to the one previously observed in hKV 7.1-7.3 channels, whereas the hKV 7.4 channel response is opposite, revealing subtype-specific responses to PUFAs. We identify a unique inner PUFA interaction site in the voltage-sensing domain of hKV 7.4 underlying the PUFA response, revealing an unconventional mechanism of modulation of hKV 7.4 by PUFAs., Competing Interests: DF, KC, JN, SL No competing interests declared, LD Reviewing editor, eLife, (© 2022, Frampton et al.)- Published
- 2022
- Full Text
- View/download PDF