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The effects of calcium antagonists on calcium overload contractures in embryonic chick myocytes induced by ouabain and veratrine
Author(s) -
Patmore Leslie,
Duncan Greig P.,
Spedding Michael
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11927.x
Subject(s) - verapamil , calcium , diltiazem , medicine , endocrinology , chemistry , tetrodotoxin , ouabain , myocyte , flunarizine , veratridine , calcium channel , sodium channel , sodium , organic chemistry
1 The protective effects of some calcium antagonists against different forms of calcium overload contracture were investigated in embryonic chick cardiac myocytes. 2 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 total inward current. Action potentials were prolonged by veratrine, automaticity was inhibited and the membrane potential depolarized from −79 to around −45 mV. 3 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. 4 Veratrine‐induced contractures were not significantly affected by 10 μ m diltiazem or verapamil. Nifedipine (5 μ m ), nimodipine (5 μ m ) and ryanodine (5 μ m ) also had little effect whilst nicardipine and flunarizine caused a concentration‐dependent inhibition of veratrine‐induced contractures with IC 50 s of 3 μ m and 2 μ m respectively. 5 Veratrine‐induced contractures were found to be very sensitive to extracellular calcium concentration with an EC 50 of 32 μ m . Edge movement associated with beating of the myocytes was much less sensitive to calcium (EC 50 = 1 m m ). Submaximal veratrine contractures in 20–50 μ m extracellular calcium were not potentiated by 1 μ m Bay K 8644. 6 Tetrodotoxin also inhibited veratrine‐induced contractures but did not affect contractions induced by ouabain in the presence of 10 μ m diltiazem. 7 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.