Polyunsaturated fatty acids modify mouse hippocampal neuronal excitability during excitotoxic or convulsant stimulation.

The n-3 polyunsaturated fatty acids (PUFAs) reduce cardiac membrane excitability and prevent cardiac arrhythmias in animals and probably in humans. In this study, we assessed the effects of n-3 PUFAs on membrane excitability in mouse hippocampal neurons with both whole-cell current and voltage-clamp methods. Extracellular application of 20 microM eicosapentaenoic acid (EPA, C20:5n-3) significantly reduced the frequency of electrical-evoked action potentials in CA1 neurons of hippocampal slices from 3.8+/-0.7 Hz of control to 2.1+/-0.5 Hz. In addition, EPA significantly hyperpolarized the resting membrane potential and raised the stimulatory threshold of action potentials in CA1 neurons. Another n-3 PUFA, docosahexaenoic acid (DHA, C22:6n-3), had effects on membrane excitability similar to those of EPA. In contrast, EPA ethyl ester, oleic acid (OA, C18:n-9), and stearic acid (SA, C18:0) did not alter the membrane excitability in CA1 neurons. Bath application of pentylenetetrazole (PTZ) or glutamate reduced the stimulatory threshold and increased the frequency of action potentials of hippocampal neurons. EPA restored PTZ- or glutamate-enhanced neuronal excitability to the control level. EPA also suppressed glutamate-activated inward currents. Furthermore, EPA and DHA significantly inhibited the frequency of action potentials without effecting the stimulatory threshold of CA3 neurons. These data demonstrate that n-3 PUFAs modify neuronal membrane excitability under control and drug-stimulated conditions. The sensitivity to these effects of PUFAs varies from neurons of different hippocampal regions.