ω-6 and ω-9 polyunsaturated fatty acids with double bonds near the carboxyl head have the highest affinity and largest effects on the cardiac IK s potassium channel.

Polyunsaturated fatty acids with double bonds closer to the head group had higher apparent affinity for IK s channels and increased IK s current more; shifting the bonds further away from the head group reduced apparent binding affinity for and effects on the IK s current. Interestingly, we found that ω-6 and ω-9 PUFAs, with the first double bond closer to the head group, left-shifted the voltage dependence of activation the most. These results allow for informed design of new therapeutics targeting IK s channels in Long QT Syndrome.