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Blockade of two voltage-dependent potassium channels, mKv1.1 and mKv1.2, by docosahexaenoic acid
J C Garratt1, M P McEvoy, D G Owen
1Wyeth Research, Taplow, Berkshire, UK.
Abstract:
The effects of the polyunsaturated fatty acid, docosahexaenoic acid, were examined on two single cloned potassium channels, mKv1.1 and mKv1.2, stably expressed in Chinese hamster ovary cells using whole-cell patch clamp techniques. Docosahexaenoic acid produced a time- and dose-dependent, reversible block of mKv1.1 and mKv1.2. Interestingly, docosahexaenoic acid increased the rate of activation of mKv1.2 leading to an enhancement of current amplitude at short intervals following activating the voltage step. This phenomenon was not seen in the case of mKv1.1. Intracellular administration of docosahexaenoic acid did not block either type of channel. These findings suggest that docosahexaenoic acid inhibits mKv1.1 and mKv1.2 channels by acting at an extracellular site and by an open-channel blocking mechanism.
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