Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs.
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.
Zhong
J
J
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, Columbia, Missouri, USA.
Hwang
T C
TC
Adams
H R
HR
Rubin
L J
LJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000096:biosynthesis / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D019446:Endotoxemia / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D004926:Escherichia coli; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006352:Heart Ventricles; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004731:Endotoxins; D008070:Lipopolysaccharides; D002118:Calcium