期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 12, 页码 4816-4821出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1221997110
关键词
fish oil; lipids; K(Ca)1.1; immunonutrition
资金
- National Institutes of Health [R01GM057654]
- Federal Ministry of Research and Education within the framework of the Center for Sepsis Control and Care [BMBF 01 EO 1002]
- German Research Foundation [DFG FOR 1738]
- National Natural Science Foundation of China [31271217]
- Key Project of Shanghai Science and Technology Commission [11JC1406400]
Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA), found abundantly in oily fish, may have diverse health-promoting effects, potentially protecting the immune, nervous, and cardiovascular systems. However, the mechanisms underlying the purported health-promoting effects of DHA remain largely unclear, in part because molecular signaling pathways and effectors of DHA are only beginning to be revealed. In vascular smooth muscle cells, large-conductance Ca2+-and voltage-activated K+ (BK) channels provide a critical vasodilatory influence. We report here that DHA with an EC50 of similar to 500 nM rapidly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit beta 1, increasing currents by up to similar to 20-fold. The DHA action is observed in cell-free patches and does not require voltage-sensor activation or Ca2+ binding but involves destabilization of the closed conformation of the ion conduction gate. DHA lowers blood pressure in anesthetized wildtype but not in Slo1 knockout mice. DHA ethyl ester, contained in dietary supplements, fails to activate BK channels and antagonizes the stimulatory effect of DHA. Slo1 BK channels are thus receptors for long-chain omega-3 fatty acids, and these fatty acids-unlike their ethyl ester derivatives-activate the channels and lower blood pressure. This finding has practical implications for the use of omega-3 fatty acids as nutraceuticals for the general public and also for the critically ill receiving omega-3-enriched formulas.
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