Veratridine activates a silent sodium channel in rat isolated aorta

Abstract

To investigate the existence of silent Na+ channels, isolated rat aorta was treated with veratridine (0.1 mM) and the resulting Ca2+ uptake was determined. After 30-min incubation the total tissue uptake of Ca2+ and Ca2+ uptake increased from 2.325 +/- 0.017 to 2.614 +/- 0.080 nmol/mg wet weight (ww) and from 162.6 +/- 9.7 to 218.1 +/- 13.0 pmol/mg ww, respectively. The veratridine-induced Ca2+ uptake was blocked by tetrodotoxin (1 microM; to 17 +/- 5%) but not altered by amiloride (10 microM-1 mM). Activation of Na+/Ca2+ exchange by Na+ removal increased Ca2+ uptake from 74.2 +/- 4.5 to 97.3 +/- 5.3 pmol/mg ww, which was suppressed by amiloride (10 microM-1 mM). Nifedipine (10 nM) and verapamil (0.1 microM) at concentrations at which depolarization-induced Ca2+ uptake was diminished did not attenuate veratridine-induced Ca2+ uptake. Phenytoin at 0.1 mM reduced the Ca2+ uptake induced by veratridine or by depolarization. R 56865 (0.1 microM) and R 59494 (1 microM), novel anti-ischemic compounds inhibiting slowly inactivating Na+ channels, suppressed the veratridine-induced but not the depolarization-induced Ca2+ uptake. Guanidinium uptake was increased by veratridine (0.1 mM) from 371.2 +/- 7.2 to 574.8 +/- 45.9 pmol/mg ww. These results suggest that the rat aorta possesses a Na+ channel which is electrically silent under normal conditions but could be activated by veratridine.