Subtype specific responses in hKv7.4 and hKv7.5 channels to polyunsaturated fatty acids

The K V 7.4 and K V 7.5 subtypes of voltage-gated potassium channels are expressed in several tissues where they play a role in physiological processes such as sound amplification in the cochlea and adjusting vascular smooth muscle tone. Therefore, the mechanisms that regulate K V 7.4 and K V 7.5 channel function are of interest. Here, we study the effect of polyunsaturated fatty acids (PUFAs) on human K V 7.4 and K V 7.5 channels expressed in Xenopus oocytes. We report that K V 7.5 is activated by PUFAs, which shift the V 50 of the conductance versus voltage (G(V)) curve towards more negative voltages. This response depends on the charge of the head group as an uncharged PUFA analogue has no effect and a positively charged PUFA analogue induces positive V 50 shifts. In contrast, we find that the K V 7.4 channel is inhibited by PUFAs, which shift V 50 towards more positive voltages. No effect on V 50 of K V 7.4 is observed by an uncharged or a positively charged PUFA analogue. Oocytes co-expressing K V 7.4 and K V 7.5 display an intermediate response to PUFAs. Altogether, the K V 7.5 channel’s response to PUFAs is like that previously observed in K V 7.1-7.3 channels, whereas the K V 7.4 channel response is opposite, revealing subtype specific responses to PUFAs.