Alterations in Ito1, IKr and Ik1 density in the BIO TO-2 strain of syrian myopathic hamsters

The BIO TO-2 strain of cardiomyopathic hamster provides a model of dilated low output heart failure. The goal of the study was to determine whether changes in potassium currents occur in this model of heart Failure. The densities of I-tol, T-Kr and I-Kl in 8-month-old myopathic hamsters were not significantly different from their age-matched controls. The half-maximum activation voltage (V 1/2) of I-Kr and I-tol, as well as the voltage-dependence of I-tol inactivation were also similar in both groups at 8 months. I-tol inactivation exhibited a double exponential time-course; the slow component (tau(2)), but not the rapid component (tau(1)), was larger in the myopathic animals. The densities of I-tol, I-Kr and I-Kl were not significantly different in the 8- and 10-month-old control animals. However, the densities of I-tol, I-Kr and I-Kl were all significantly lower in the 10-month-old myopathlc hamsters relative to the 10-month-old controls. The V 1/2 for I-Kr and I-tol activation was the same in myopathic and control animals. tau(2), but not tau(1), of I-tol inactivation was again larger in the myopathic animals. The voltage-dependence of I(tol)ivation was shifted slightly, but significantly, positive in the myopathic animals. Lastly, a sustained outwardly rectifying current that activated upon depolarization was found to be larger in the myopathic animals at both 8 and 10 months of age. In conclusion, many of the alterations in potassium current densities in the 10-month-old cardiomyopathic hamsters are qualitatively similar to the changes observed in the failing human heart. (C) 1997 Academic Press Limited.