[Underlying mechanism for prolongation of action potential duration in ventricular cardiomyocytes of rats suffered from thermal injury].
Severe thermal injury causes prolongation of action potential duration (APD) in cardiomyocytes, which results in cardiac dysfunction by inducing disturbance of calcium dyshomeostasis in cardiac myocytes. However, the underlying mechanism for APD prolongation remains unclear. In the present study, we examined the major action potential repolarization-related ion channel currents in rat ventricular cardiomyocytes, including transient outward potassium current (I(to)), inward rectifier potassium current (I(K1)) and L-type Ca(2+) current (I(Ca-L)) to investigate the alterations of these currents, which might account for the pathogenesis of APD prolongation induced by thermal injury. Twelve hours after approximately 40% of the total body surface area, full-thickness (third-degree) cutaneous thermal injury was produced in rats, ventricular cardiomyocytes were isolated from the hearts with systolic and diastolic dysfunction. APD was found to be markedly prolonged, while APD(50) and APD(90) in ventricular cardiomyocytes from rats with thermal injury were (46.02+/-3.78) ms and (123.24+/-12.48) ms (n=19), respectively, significantly longer than (23.28+/-4.85) ms and (72.12+/-3.57) ms (n=17, P<0.01) in ventricular cardiomyocytes from sham rats. Thermal injury remarkably suppressed Ito density in ventricular cardiomyocytes. Ito density at +60 mV was decreased from (34.15+/-3.78) pA/pF (n=20) in sham group to (20.39+/-1.98) pA/pF (n=25, P<0.01) in thermal injury group, and the decrease extended from -30 to +60 mV. Similarly, current densities of I(K1) from -120 to -80 mV in thermal injury group were also significantly lower than that in sham group. In contrast, we failed to detect any alterations in I(Ca-L) density, and voltage-dependence of activation and inactivation in thermal injury group, compared with that in sham group. Taken together, our data suggest that thermal injury results in function downregulation of transient outward potassium channels and inward rectifier potassium channels, which contributes, at least in part, to APD prolongation and subsequent cardiac dysfunction.
Deng
Jian-Xin
JX
Department of Pathophysiology, Key Laboratory of Shock and Microcirculation of Guangdong Province, Southern Medical University, Guangzhou 510515, China.
Liu
Jie
J
D000200:Action Potentials; D000818:Animals; D002056:Burns / Q000503:physiopathology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D005260:Female; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016276:Ventricular Function
D020746:Calcium Channels, L-Type; D024661:Potassium Channels, Inwardly Rectifying