[Alterations of cardiac hemodynamics, sodium current and L-type calcium current in rats with L-thyroxine-induced cardiomyopathy].
The aim of the present study is to investigate the alterations of cardiac hemodynamics, sodium current (I(Na)) and L-type calcium current (I(Ca-L)) in the cardiomyopathic model of rats. The model of cardiomyopathy was established by intraperitoneal injection of L-thyroxine (0.5 mg/kg) for 10 d. The hemodynamics was measured with biological experimental system, and then I(Na) and I(Ca-L) were recorded by using whole cell patch clamp technique. The results showed that left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), +/-dp/dt(max) in cardiomyopathic group were significantly lower than those in the control group, while left ventricular end-diastolic pressure (LVEDP) in cardiomyopathic group was higher than that in the control group. Intraperitoneal injection of L-thyroxine significantly increased the current density of I(Na) [(-26.2+/-3.2) pA/pF vs (-21.1+/-6.3) pA/pF, P<0.01], shifted steady-state activation and inactivation curves negatively, and markedly prolonged the time constant of recovery from inactivation. On the other hand, the injection of L-thyroxine significantly increased the current density of I(Ca-L) [(-7.9+/-0.8) pA/pF vs (-5.4+/-0.6) pA/pF, P<0.01)], shifted steady-state activation and inactivation curves negatively, and obviously shortened the time constant of recovery from inactivation. In conclusion, the cardiac performance of cardiomyopathic rats is similar to that of rats with heart failure, in which the current density of I(Na) and especially the I(Ca-L) are enhanced, suggesting that calcium channel blockade and a decrease in Na(+) permeability of membrane may play an important role in the treatment of cardiomyopathy.
Wang
Jing
J
Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Zhang
Wei-Dong
WD
Lin
Mu-Sen
MS
Zhai
Qing-Bo
QB
Yu
Feng
F
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D013974:Thyroxine
D020746:Calcium Channels, L-Type; D015222:Sodium Channels; D013974:Thyroxine