Estudios científicos

Inhibition of cardiac voltage-gated sodium channels by grape polyphenols


BACKGROUND AND PURPOSE: The cardiovascular benefits of red wine consumption are often attributed to the antioxidant effects of its polyphenolic constituents, including quercetin, catechin and resveratrol. Inhibition of cardiac voltage-gated sodium channels (VGSCs) is antiarrhythmic and cardioprotective. As polyphenols may also modulate ion channels, and possess structural similarities to several antiarrhythmic VGSC inhibitors, we hypothesised that VGSC inhibition may contribute to cardioprotection by these polyphenols.
EXPERIMENTAL APPROACH: The whole-cell voltage-clamp technique was used to record peak and late VGSC currents (INa) from recombinant human heart NaV1.5 channels expressed in tsA201 cells. Right ventricular myocytes from rat heart were isolated and single myocytes were field-stimulated. Either calcium transients or contractility were measured using the calcium-sensitive dye Calcium-Green 1AM or video edge detection, respectively.
KEY RESULTS: The red grape polyphenols quercetin, catechin and resveratrol blocked peak INa with IC50s of 19.4 microM, 76.8 microM and 77.3 microM, respectively. In contrast to lidocaine, resveratrol did not exhibit any frequency-dependence of peak INa block. Late INa induced by the VGSC long QT mutant R1623Q was reduced by resveratrol and quercetin. Resveratrol and quercetin also blocked late INa induced by the toxin, ATX II, with IC50s of 26.1 microM and 24.9 microM, respectively. In field-stimulated myocytes, ATXII-induced increases in diastolic calcium were prevented and reversed by resveratrol. ATXII-induced contractile dysfunction was delayed and reduced by resveratrol.
CONCLUSIONS AND IMPLICATIONS: Our results indicate that several red grape polyphenols inhibit cardiac VGSCs and that this effect may contribute to the documented cardioprotective efficacy of red grape products.

Comentarios divulgativos:

Los beneficios cardiovasculares del consumo de vino tinto se suelen atribuir a los efectos antioxidantes de sus componentes polifenólicos, como la quercetina, catequina y el resveratrol. La inhibición de los canales cardíacos dependientes de sodio y de voltaje (VGSCs) es antiarrítmico y cardioprotector. Como los polifenoles también pueden modular los canales de iones, y poseen similitudes estructurales con varios antiarrítmicos e inhibidores de los VGSC, planteamos la hipótesis de que la inhibición de VGSC puede contribuir a la cardioprotección por estos polifenoles.
La técnica de tensión-por pinza se utiliza para registrar las corrientes de pico y fines de VGSC (INA) del corazón humano La uva roja contiene polifenoles como laquercetina, catequina y el resveratrol que bloquea el pico INa con IC50 de 19,4 microM, 76,8 y 77,3 microM microM, respectivamente. En contraste a la lidocaína, el resveratrol no mostraba la frecuencia de la dependencia del pico
Nuestros resultados indican que varios de los polifenoles de la uva roja inhiben VGSCs y que este efecto podría contribuir a la eficacia +cardioprotector ade los productos de la uva roja.