Effects of Ca channel blockers on Ca loading induced by metabolic inhibition and hyperkalemia in cardiomyocytes |
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Authors: | Tianlai Tang Rose Duffield Andrew K S Ho |
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Institution: | Division of Clinical Pharmacology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, One Illini Dr., Peoria, IL 61605, USA |
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Abstract: | The effects of the L-type (nifedipine and verapamil) and the T-type (mibefradil) Ca2+ channel blockers on the increase in intracellular Ca2+ concentration (Ca2+]i) induced by NaCN metabolic inhibition and hyperkalemia were examined in chicken cardiomyocytes using fluorescence imaging with Fura-2. NaCN induced a slow and sustained rise in Ca2+]i, which was not affected by pretreating the cells for 5 min with nifedipine, verapamil, or mibefradil at 100 nM or 10 μM. Pretreatment of the cells with 10 μM nifedipine, verapamil, or mibefradil for 5 min remarkably inhibited the K+-induced increase in Ca2+]i. These inhibitory effects diminished after 48-h pretreatment with nifedipine or verapamil but not with mibefradil. Ryanodine also induces an increase in Ca2+]i, and this effect was enhanced by 48-h pretreatment of the cells with 10 μM verapamil but not with 10 μM mibefradil. We conclude that the NaCN-induced increase in Ca2+]i is independent of the Ca2+ influx though the L-type or T-type Ca2+ channels. Chronic inhibition of the L-type Ca2+ channels but not T-type channels may enhance the ryanodine receptor-mediated Ca2+ release, which may be responsible for the development of tolerance to their inhibitory effects on K+-induced increase in Ca2+]i. |
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Keywords: | metabolic inhibition hyperkalemia heart muscle cell calcium channel blocking agent calcium ion |
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