Carnosine is a novel peptide modulator of intracellular calcium and
contractility in cardiac cells.
Zaloga, Gary P., Pamela R. Roberts, Kimberly W. Black, Marina Lin,
Gisele Zapata-Sudo, Roberto T. Sudo, Thomas E. Nelson.
Department of Anesthesia, Bowman Gray School of Medicine,Wake
Forest University, Winston-Salem, NC 27157-1009. Visiting scholars
from the Department of Basic and Clinical Pharmacology, Universidade
Federal de Rio de Janeiro, Rio de Janeiro, Brazil
APStracts 3:0345H, 1996.
Myocardial contractile failure is a common cause of morbidity and
mortality in patients with ischemic heart disease and systemic
inflammatory states such as sepsis. Accumulating evidence indicates
that contractile failure is associated with dysregulation of
myoplasmic calcium levels. In a search for biochemical causes for
contractile dysfunction, we found that the dipeptide carnosine
improves cardiac contractility and tested the possibility that
carnosine plays a role in the regulation of intracellular calcium.
Carnosine increased contractility in a dose-dependent manner (1-10
mM) in isolated perfused rat hearts and it also increased free
intracellular calcium levels in isolated myocytes. Carnosine
increased myocyte tension via calcium release from the ryanodine
receptor calcium release channel in skinned myocardial fibers and
increased open state probability and dwelltime of the isolated
ryanodine receptor calcium release channel in lipid bilayers. In
addition, we report that carnosine sensitizes the contractile
proteins to calcium. These results suggest a novel role for carnosine
as a modulator of intracellular calcium and contractility in cardiac
tissue.
Received 22 March 1996; accepted in final form 31 July 1996.
APS Manuscript Number H275-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996