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The effects of calcium antagonists on calcium overload contractures in embryonic chick myocytes induced by ouabain and veratrine

, : The effects of calcium antagonists on calcium overload contractures in embryonic chick myocytes induced by ouabain and veratrine. British Journal of Pharmacology 97(1): 83-94

The protective effects of some calcium antagonists against different forms of calcium overload contracture were investigated in embryonic chick cardiac myocytes. Tetrodotoxin-sensitive sodium currents were recorded from the myocytes by the whole-cell voltage-clamp technique. Although the peak current was attenuated by veratrine, the inactivation process was markedly inhibited, resulting in a large increase in the the total inward current. Action potentials were prolonged by veratrine, automaticity was inhibited and the membrane potential depolarized from -79 to around -45 mV. Measurements of contraction were made from aggregates of myocytes using a video edge detection technique which quantified edge movement. Veratrine caused an initial positive inotropism then inhibited automaticity of aggregates with subsequent development of a tonic contracture to around 300% of the twitch contraction. Veratrine-induced contractures were not significantly affected by 10 .mu.M diltiazem or verapamil. Nifedipine (5 .mu.M), nimodipine (5 .mu.M) and ryanodine (5 .mu.M) also had little effect whilst nicardipine and flunarizine caused a concentration-dependent inhibition of veratrine-induced contractures with IC50 s of 3 .mu.M and 2 .mu.M respectively. Veratrine-induced contractures were found to be very sensitive to extracellular calcium concentration with an EC50 of 32 .mu.M. Edge movement associated with beating of the myocytes was much less sensitive to calcium (EC50 = 1 mM). Submaximal veratrine contractures in 20-50 .mu.M extracellular calcium were not potentiated by 1 .mu.M Bay K 8644. Tetrodotoxin also inhibited veratrine-induced contractures but did not affect contractions induced by ouabain in the presence of 10 diltiazem. Ouabain-induced contractures were also inhibited by nicardipine and flunarizine indicating that these drugs can protect against calcium overload in embryonic chick heart by a mechanism independent of the normal form of voltage-sensitive sodium or calcium channels.


PMID: 2470461

DOI: 10.1111/j.1476-5381.1989.tb11927.x

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