Digoxin- and monensin-induced changes of intracellular Ca2+ concentration in isolated guinea-pig ventricular myocyte.
This study was undertaken to determine the possible mechanisms of actions of monensin and digoxin by using isolated guinea-pig ventricular myocytes. Since Ca2+ is the major signal for triggering contraction of cardiac muscle, the objective of this study was to determine whether monensin and digoxin affect the [Ca2+]i of cardiac myocytes and if so is this effect due to an increase in [Na+]i. Three different concentrations of digoxin (0.3, 1 and 3 micromol/l) and three different concentrations of monensin (0.3, 1 and 3 micromol/l) were used. Each treatment was monitored for two hours by using computerized fluoroscopy. Both digoxin and monensin increased the [Ca2+]i and accelerated the onset time of [Ca2+]i increase in a dose-dependent manner. Normal myocytes (loaded with fura-2 for 30 min before the treatment) were also compared with 'weakened' myocytes (loaded with fura-2 for 3 h before the treatment to create a 'weakened' condition). It was found that although 0.3 micromol/l monensin and digoxin did not change the [Ca2+]i in normal myocytes, they increased the [Ca2 +]i in 'weakened' myocytes. Finally, a Na+-free medium was used to demonstrate the effect of [Na+]o on both monensin- and digoxin-induced increases in [Ca2+]i. It was found that digoxin did not increase the [Ca2+]i in the Na+-free medium. Although monensin increased the [Ca2+]i in the Na+-free solution, this increase was not as large as in the Na+-containing medium. The results of the study led to the conclusion that the positive inotropic effect of digoxin depends on [Na+]o. However, monensin increases [Ca2+]i in Na+-dependent and -independent ways. An addition conclusion was that 'weakened' myocytes are more sensitive to the monensin and digoxin treatment than normal myocytes.
Meral
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Yuzuncu Yil Universitesi, Veteriner Fakultesi, Fizyoloji Anabilim Dali, Van, Turkey. imeral20@hotmail.com
Hsu
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Hembrough
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004077:Digoxin / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008985:Monensin / Q000008:administration & dosage / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D002316:Cardiotonic Agents; D004077:Digoxin; D008985:Monensin; D002118:Calcium