Blocking effects of polyunsaturated fatty acids on Na+ channels of neonatal rat ventricular myocytes
1995
Xiao, Y.F. | Kang, J.X. | Morgan, J.P. | Leaf, A.
Recent evidence indicates that polyunsaturated long-chain fatty acids (PUFAs) prevent lethal ischemia-induced cardiac arrhythmias in animals and probably in humans. To increase understanding of the mechanism(s) of this phenomenon, the effects of PUFAs on Na+ currents were assessed by the whole-cell patch-clamp technique in cultured neonatal rat ventricular myocytes. Extracellular application of the free 5,8,11,14,17-eicosapentaenoic acid (EPA) produced a concentration-dependent suppression of ventricular, voltage-activated Na+ currents (I(Na)). After cardiac myocytes were treated with 5 or 10 micromolar EPA, the peak I(Na) (elicited by a single-step voltage change with pulses from -80 to -30 mV) was decreased by 51% +/- 8% (P < 0.01; n = 10) and 64% +/- 5% (P < 0.001; n = 21), respectively, within 2 min. Likewise, the same concentrations of 4,7,10,16,19-docosahexsenoic acid produced the same inhibition of I(Na). By contrast, 5 and 10 micromolar arachidonic acid (AA) caused less inhibition of I(Na), but both n-6 and n-3 PUFAs inhibited I(Na) significantly. A monounsaturated fatty acid and a saturated fatty acid did not. After washing out EPA, I(Na) returned to the control level. Raising the concentration of EPA to 40 micromolar completely blocked I(Na). The IC50 of EPA was 4.8 micromolar. The inhibition of this Na+ channel was found to be dose and time, but not use dependent. Also, the EPA-induced inhibition of I(Na) was voltage dependent, since 10 micromolar EPA produced 83% +/- 7% and 29% +/- 5% inhibition of I(Na) elicited by pulses from -80 to -30 mV and from -150 to -30 mV, respectively, in single-step voltage changes. A concentration of 10 micromolar EPA shifted the steady-state inactivation curve of I(Na) by -19 +/- 3 mV (n = 7; P < 0.01). These effects of PUFAs on I(Na) may be important for their antiarrhythmic effect in vivo.
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