Omega-3 Fatty Acids Activate Slo1 BK Channels and Lower Blood Pressure

Abstract

Long-chain omega-3 fatty acids such as docosahexaenoic acid (DHA) found in oily fish may offer various health benefits but the underling mechanisms are only poorly understood. In vascular smooth muscle cells, large-conductance Ca2+- and voltage-dependent K+ (Slo1 BK) channels provide a vasodilatory influence. We found that DHA with EC50 of ∼500 nM directly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit β1 in excised-patches, increasing currents by up to ∼20-fold. The DHA action does not require voltage-sensor activation or Ca2+ binding but depends on an electrostatic interaction within 1 or 4. DHA acutely lowers blood pressure in anesthetized wild-type but not in Slo1 knockout mice. DHA ethyl ester (DHA EE), found in dietary supplements, fails to activate BK channels and antagonizes the stimulatory effect of DHA. On an equimolar basis, the stimulatory effect DHA on Slo+1 channels was greater than that of eicosapentaenoic acid, alpha-linolenic acid, arachidonic acid, or linoleic acid. Slo1 BK channels are thus receptors for long-chain omega-3 fatty acids that, unlike their ethyl ester derivatives, activate the channels and lower blood pressure. Supported in part through the NIH, DFG FOR 1738, and Shanghai Science and Technology Commission.