Veratridine-induced intoxication in the isolated left atrium of the rat - effects of some antiischemic compounds

Veratridine-induced Na+ and Ca2+ uptake was used as a simulation of ischemia-induced Na+ and Ca2+ uptake. Therefore, electrically driven (1 Hz) isolated left atria of the rat were intoxicated with veratridine and the Ca-45(2+) uptake was determined. Veratridine (10(-4) mol/l) increased the Ca-45(2+) uptake from 575 +/- 13 to 2320 +/- 86 dpm/mg ww (n = 20). The total tissue content of Ca-45 was elevated from 4328 +/- 132 to 5136 +/- 303 dpm/mg ww (n = 13). The veratridine-induced Ca-45(2+) uptake was completely suppressed by tetrodotoxin (10(-7) and 10(-6) mol/l), whereas amiloride (6.10(-6) mol/l) and phentolamine (10(-6) and 10(-5) mol/l) exhibited no effect on the veratridine-induced Ca-45(2+) uptake. Nifedipine (10(-7) and 10(-6) mol/l) was ineffective on veratridine-induced Ca-45(2+) uptake. Verapamil (10(-5) mol/l) suppressed the veratridine-induced Ca-45(2+) uptake, but the Ca-45(2+) uptake in the absence of veratridine was also suppressed by verapamil (10(-6) and 10(-5) mol/l). The novel anti-ischemic compounds R 56865 (10(-8)-10(-5) mol/l) and R 59494 (10(-8)-10(-5) mol/l) totally abolished veratridine-induced Ca-45(2+) uptake.

It is speculated that Ca2+ enters the cell via a Na+ channel which changes its selectivity upon veratridine treatment. Consequently, R 56865 and R 59494 could display their protective effect by either inhibiting the modified Na+ channel or preventing the transition of the normal Na+ channel to its altered state. As ischemia- and veratridine-induced Na+ and Ca2+ uptake share some similarities, it is proposed that veratridine-induced Ca-45(2+) uptake of the isolated left atrium of the rat could be used to study the mechanism of action of novel anti-ischemic drugs.