Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca²âº-dependent K⁺ channels.

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 Ca(2+)- and voltage-activated K(+) (BK) channels provide a critical vasodilatory influence. We report here that DHA with an EC50 of ∼500 nM rapidly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit ß1, increasing currents by up to ∼20-fold. The DHA action is observed in cell-free patches and does not require voltage-sensor activation or Ca(2+) binding but involves destabilization of the closed conformation of the ion conduction gate. DHA lowers blood pressure in anesthetized wild-type 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.

Impairments of behavior, information flow between thalamus and cortex, and prefrontal cortical synaptic plasticity in an animal model of depression.

Growing evidence suggests the involvement of stress in the pathophysiology of depression. This study was designed to test behavioral and electrophysiological changes in a stressed model of depression. Rats were randomly divided into control and stressed groups. Chronic unpredictable stress combined with isolation rearing was applied in rats of stressed group for three weeks. Weight and sucrose consumption were measured during the model establishing period. Behavior was measured by Morris water maze. Electroencephalography (EEG) of thalamus and prefrontal cortex was recorded after behavioral tests, followed by recording long-term potentiation (LTP) of the same thalamocortical pathway. Results showed that rats' weight and sucrose intake were significantly lower in stressed group than those in control group. In stressed group, escape latency of reversal training stage in water maze test was significantly prolonged, and platform crossings of reversal probe trials were significantly decreased. EEG test showed that the extent of thalamus driving prefrontal cortex was decreased in stressed group. LTP test showed lower postsynaptic potential amplitude in stressed group as compared to that in control group. In conclusion, chronic stress could cause certain behavioral changes in rats, with possible mechanism of impairing EEG of certain thalamocortical pathway and prefrontal cortical synaptic plasticity.