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Browsing by Author "Hsu, W"

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    Article
    Digoxin- and Monensin-Induced Changes of Intracellular Ca2+ Concentration in Isolated Guinea-Pig Ventricular Myocyte
    (Wiley, 2002) Meral, I; Hsu, W; Hembrough, FB
    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 mu mol/l) and three different concentrations of monensin ( 0.3, 1 and 3 mu mol/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 [ Ca 2+] 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 mu mol/l monensin and digoxin did not change the [ Ca 2+] 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 [ Ca 2+] i. It was found that digoxin did not increase the [ Ca 2+] i in the Na+- free medium. Although monensin increased the [ Ca 2+] 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 [ Ca 2+] 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.
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    Functional Changes in Isolated Guinea-Pig Papillary Muscle Induced by Monensin and Digoxin
    (Blackwell verlag Gmbh, 2002) Meral, I; Hembrough, FB; Bailey, TB; Hsu, W
    The effects of digoxin and monensin on contraction force (CF), initial contraction velocity (ICV), average contraction velocity (ACV), initial relaxation velocity (IRV) and stimulus to response time (ST) in 'fatigued' (tired) and 'non-fatigued' (fresh) guinea-pig papillary muscles were investigated. 'Fatigued' muscles had lost 30% of their original CF with the elapse of tune before they were treated. The 5 h of measurement were divided into five periods (TO was equilibration, T1, T2, T3 and T4 were, respectively, 1, 2, 3 and 4 h after drug administration). It was found that both monensin and digoxin increased the CF, ICV and ACV at T1 and increased the IRV at T2. Digoxin lost its effect with the elapse of time while monensin did not. Digoxin also decreased the ST at T2, T3 and T4. However, monensin did not change the ST. It was also found that 'fatigued' and 'non-fatigued' guinea-pig papillary muscles did not respond to the drug treatment differently. It was concluded that the initial effects of these two drugs on guinea-pig papillary muscles are similar regarding contractility but in time digoxin loses its effect while monensin does not.