Activated complement directly modifies the performance of isolated heart muscle cells from guinea pig and rat.
The complement system has been implicated in the pathogenesis of cardiovascular disorders including ischemia and atherosclerosis. Selective deposition of C5b-9, the membrane attack complex of complement, has been histochemically documented in human myocardium early after reperfusion of ischemic areas and in infarcted zones. However, functional sequelae of the C5b-9 complex binding to myocardial cells have not been identified. Insertion of C5b-9 complexes into the membrane of other cell types can generate transient changes in membrane permeability in the absence of cell lysis. We demonstrate in beating isolated adult guinea pig and rat cardiac myocytes that human derived C5b-9 can transiently augment in a dose-dependent manner both basal cytosolic calcium concentration and calcium transients, resulting in a temporary increase in contractility. If similar changes occur in human heart cells in vivo, they could significantly affect myocardial performance and contribute to functional abnormalities seen in ischemia and other pathological conditions associated with complement activation.
Berger
H J
HJ
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Taratuska
A
A
Smith
T W
TW
Halperin
J A
JA
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002469:Cell Separation; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015938:Complement Membrane Attack Complex; D003402:Creatine Kinase; D002118:Calcium