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Am J Physiol Heart Circ Physiol 273: H2312-H2324, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 5, H2312-H2324, November 1997

Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs

Juming Zhong1, Tzyh-Chang Hwang2,3, H. Richard Adams1,3, and Leona J. Rubin1,3

1 Department of Veterinary Biomedical Sciences, College of Veterinary Medicine; 2 Department of Physiology, School of Medicine; and the 3 Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211

The circulatory response to gram-negative sepsis and its experimental counterpart, endotoxemia, includes a profound dysfunction in myocardial contractility that is resident to the myocyte and associated with reduced systolic free intracellular Ca2+ concentration ([Ca2+]i). We explored the possibility that decreased systolic [Ca2+]i in endotoxemic myocytes is correlated with reduced L-type Ca2+ current (ICa,L). Ventricular myocytes were isolated from guinea pigs 4 h after an intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 4 mg/kg). Membrane potentials and Ca2+ currents were measured using whole cell patch-clamp methods. The action potential duration of endotoxemic myocytes was significantly shorter than control values (time to 50% repolarization: LPS, 314 ± 23 ms; control, 519 ± 36 ms, P < 0.05). Correspondingly, endotoxemic myocytes demonstrated significantly reduced peak ICa,L density (3.5 ± 0.2 pA/pF) and Ba2+ current (IBa) density (7.3 ± 0.5 pA/pF) compared with respective values of control myocytes (ICa,L density 6.1 ± 0.3 pA/pF, IBa density 11.3 ± 0.8 pA/pF; P < 0.05). Endotoxemia-induced reduction in peak ICa,L could not be attributed to alterations in current-voltage relationships, steady-state activation and inactivation, or recovery from inactivation. The beta -adrenoceptor agonist isoproterenol, but not the Ca2+ channel activator BAY K 8644, reversed the LPS-induced reduction in peak ICa,L, cell contraction, and systolic [Ca2+]i. These data demonstrate that part of the host response to endotoxemia involves diminished sarcolemmal ICa,L of ventricular myocytes.

myocytes; endotoxin; excitation-contraction coupling; isoproterenol; BAY K 8644


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