Veratridine activates a silent sodium channel in rat isolated aorta.
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.
Wermelskirchen
D
D
Janssen Research Foundation, Neuss, Germany.
Wilffert
B
B
Nebel
U
U
Leidig
A
A
Wirth
A
A
Peters
T
T
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism*; D019791:Guanidine; D006146:Guanidines / Q000378:metabolism; D066298:In Vitro Techniques; D010880:Piperidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*
D052160:Benzothiazoles; D006146:Guanidines; D010880:Piperidines; D011758:Pyrroles; D015222:Sodium Channels; D013844:Thiazoles; D014665:Vasodilator Agents; C072538:R 59494; D013779:Tetrodotoxin; D014701:Veratridine; D000584:Amiloride; C054551:R 56865; D019791:Guanidine; D002118:Calcium