KCNE1 tunes the sensitivity of K_V7.1 to polyunsaturated fatty acids by moving turret residues close to the binding site.

ABSTRACT: The voltage-gated potassium channel K_V7.1 and the auxiliary subunit KCNE1 together form the cardiac I_Ks channel, which is a proposed target for future anti-arrhythmic drugs. We previously showed that polyunsaturated fatty acids (PUFAs) activate K_V7.1 via an electrostatic mechanism. The activating effect was abolished when K_V7.1 was co-expressed with KCNE1, as KCNE1 renders PUFAs ineffective by promoting PUFA protonation. PUFA protonation reduces the potential of PUFAs as anti-arrhythmic compounds. It is unknown how KCNE1 promotes PUFA protonation. Here, we found that neutralization of negatively charged residues in the S5-P-helix loop of K_V7.1 restored PUFA effects on K_V7.1 co-expressed with KCNE1 in Xenopus oocytes.

SUBMITTER: Larsson JE 

PROVIDER: S-EPMC6080945 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature