BLOCKADE OF 2 VOLTAGE-DEPENDENT POTASSIUM CHANNELS, MKV1.1 AND MKV1.2, BY DOCOSAHEXAENOIC ACID

The effects of the polyunsaturated fatty acid, docosahexaenoic acid, w ere examined on two single cloned potassium channels, mKv1.1 and mKv1. 2, stably expressed in Chinese hamster ovary cells using whole-cell pa tch clamp techniques. Docosahexaenoic acid produced a time- and dose-d ependent, reversible block of mKv1.1 and mKv1.2. Interestingly, docosa hexaenoic acid increased the rate of activation of mKv1.2 leading to a n enhancement of current amplitude at short intervals following activa ting the voltage step. This phenomenon was not seen in the case of mKv 1.1 Intracellular administration of docosahexaenoic acid did not block either type of channel. These findings suggest that docosahexaenoic a cid inhibits mKv1.1 and mKv1.2 channels by acting at an extracellular site and by an open-channel blocking mechanism.