Depression of L-type Ca2+ and transient outward K+ currents in endotoxin-treated rat cardiac myocytes

ABSTRACT

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 Ca2+ and K+ currents in cardiac myocytes from endotoxin-treated rat. Ventricular myocytes were isolated from normal and endotoxemic rats (ex vivo), that were treated for 10 hours with Salmonella enteritidis lipopolysaccharides (LPS; 1.5 mg/kg) intravenously. Normal cardiac myocytes were also incubated for 6 hours with 200 ng/ml LPS (in vitro). L-type Ca2+ current (ICa,L) and transient outward K+ current (Ito) were measured using whole cell patch clamp techniques. Peak ICa,L was reduced in endotoxemic myocytes (ex vivo; 6.00.4 pA/pF, P<0.01) compared to normal myocytes (control; 10.90.6 pA/pF). Exposure to endotoxin in vitro also attenuated ICa,L (8.40.4 pA/pF, P<0.01). The amplitude of Ito on depolarization to 60 mV was reduced in endotoxin treated myocytes (16.51.5 pA/pF, P<0.01, ex vivo; 20.00.9 pA/pF, P<0.01, in vitro) compared to normal myocytes (control; 24.71.0 pA/pF). There was no voltage shift in steady-state inactivation of ICa,L and Ito between groups. These results suggest that endotoxin reduces Ca2+ and K+ currents of rat cardiac myocytes, which may lead to cardiac dysfunction.