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 Ito1, IKr and IK1 in 8-month-old myopathic hamsters were not significantly different from their age-matched controls. The half-maximum activation voltage (V1/2) of IKr and Ito1, as well as the voltage-dependence of Ito1 inactivation were also similar in both groups at 8 months. Ito1 inactivation exhibited a double exponential time-course; the slow component (tau2), but not the rapid component (tau1), was larger in the myopathic animals. The densities of Ito1, IKr and IK1 were not significantly different in the 8- and 10-month-old control animals. However, the densities of Ito1, IKr and IK1 were all significantly lower in the 10-month-old myopathic hamsters relative to the 10-month-old controls. The V1/2 for IKr and Ito1 activation was the same in myopathic and control animals. tau2, but not tau1, of Ito1 inactivation was again larger in the myopathic animals. The voltage-dependence of Ito1 inactivation 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.
Lodge
N J
NJ
Cardiovascular Drug Discovery, Bristol-Myers Squibb PRI, Princeton, NJ 08543-4000, USA.
Normandin
D E
DE
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D048429:Cell Size; D006224:Cricetinae; D051668:Delayed Rectifier Potassium Channels; D004195:Disease Models, Animal; D004594:Electrophysiology; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008647:Mesocricetus; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D024683:Potassium Channels, Tandem Pore Domain; D024642:Potassium Channels, Voltage-Gated; D014655:Vascular Resistance
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024683:Potassium Channels, Tandem Pore Domain; D024642:Potassium Channels, Voltage-Gated