Veratridine-induced intoxication in the isolated left atrium of the rat: Effects of some anti-ischemic compoundsWermelskirchen, D., Wilffert, B., Nebel, U., Wirth, A. & Peters, T., 22-Oct-1991, In : Naunyn-Schmiedeberg's Archives of Pharmacology. 344, 1, p. 101-106 6 p.
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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 the45Ca2+uptake was determined. Veratridine (10-4mol/l) increased the45Ca2+uptake from 575 ± 13 to 2320 ± 86 dpm/mg ww (n = 20). The total tissue content of45Ca was elevated from 4328 ± 132 to 5136 ± 303 dpm/mg ww (n 13). The veratridine-induced45Ca2+uptake was completely suppressed by tetrodotoxin (10-7and 10-6mol/l), whereas amiloride (6 · 10-6mol/l) and phentolamine (10-6and 10-5mol/l) exhibited no effect on the veratridine-induced45Ca2+uptake. Nifedipine (10-7and 10-6mol/l) was ineffective on veratridine-induced45Ca2+uptake, but the45Ca2+uptake in the absence of veratridine was also suppressed by verapamil (10-6and 10-5mol/l). The novel anti-ischemic compounds R 56865 (10-8- 10-5mol/l) and R 59494 (10-8- 10-5mol/l) totally abolished veratridine-induced45Ca2+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-induced45Ca2+uptake of the isolated left atrium of the rat could be used to study the mechanism of action of novel anti-ischemic drugs.
|Number of pages||6|
|Journal||Naunyn-Schmiedeberg's Archives of Pharmacology|
|Publication status||Published - 22-Oct-1991|
- 45Ca2+uptake, Myocardium, Na+channel, Veratridine, amiloride, calcium 45, cardiovascular agent, n [1 [4 (4 fluorophenoxy)butyl] 4 piperidinyl] n methyl 2 benzothiazolamine, n methyl n [1 (4 phenoxybutyl) 3 pyrrolidinyl] 2 benzothiazolamine, nifedipine, phentolamine, r 59494, sodium channel, tetrodotoxin, unclassified drug, verapamil, veratridine, animal tissue, article, calcium transport, concentration response, controlled study, electrostimulation, heart left atrium, intoxication, male, nonhuman, priority journal, rat