Depression of L-type Ca<SUP>2&#8290;</SUP> and Transient Outward K<SUP>&#8290;</SUP> Currents in Endotoxin-treated Rat Cardiac Myocytes

Depression of L-type Ca<SUP>2&#8290;</SUP> and Transient Outward K<SUP>&#8290;</SUP> Currents in Endotoxin-treated Rat Cardiac Myocytes

<P> Decreased cardiac contractility occurs in endotoxicosis, but little is known about the ionic mechanism responsible for myocardial dysfunction. In this study, we examined the changes in Ca<SUP>2&#8290;</SUP> and K<SUP>&#8290;</SUP> currents in cardiac myocytes from endotoxin-treated rat. Ventricular myocytes were isolated from normal and endotoxemic rats (<I>ex vivo</I>), that were treated for 10 hours with <I>Salmonella enteritidis</I> lipopolysaccharides (LPS; 1.5 mg/kg) intravenously. Normal cardiac myocytes were also incubated for 6 hours with 200 ng/ml LPS (<I>in vitro</I>). L-type Ca<SUP>2&#8290;</SUP> current (I<SUB>Ca,L</SUB>) and transient outward K<SUP>&#8290;</SUP> current (I<SUB>to</SUB>) were measured using whole cell patch clamp techniques. Peak I<SUB>Ca,L</SUB> was reduced in endotoxemic myocytes (<I>ex vivo</I>; 6.00.4 pA/pF, P＜0.01) compared to normal myocytes (control; 10.90.6 pA/pF). Exposure to endotoxin <I>in vitro</I> also attenuated I<SUB>Ca,L</SUB> (8.40.4 pA/pF, P＜0.01). The amplitude of I<SUB>to</SUB> on depolarization to 60 mV was reduced in endotoxin treated myocytes (16.51.5 pA/pF, P＜0.01, <I>ex vivo</I>; 20.00.9 pA/pF, P＜0.01 , <I>in vitro</I>) compared to normal myocytes (control; 24.71.0 pA/pF). There was no voltage shift in steady-state inactivation of I<SUB>Ca,L</SUB> and I<SUB>to</SUB> between groups. These results suggest that endotoxin reduces Ca<SUP>2&#8290;</SUP> and K<SUP>&#8290;</SUP> currents of rat cardiac myocytes, which may lead to cardiac dysfunction.