We
review cytosolic free calcium (Cai) measurements in hypoxic single
cardiomyocytes, isolated heart tissue and intact myocardium. In single cells the seminal event may be a
shortening which is (largely) Cai-independent and probably
corresponds to hypoxic contracture of intact tissue. This shortening is soon followed by a Cai
rise and net Ca2+ ingress across the sarcolemma which is sensitive
to the Na+ electrochemical gradient, suggesting that na-Ca exchange
occurs, and that a Nai imbalance precedes the Cai rise. Reoxygenation of single cells triggers
spontaneous mechanical activity (and oscillation of Ca2+ between
cytosol and sarcoplasmic reticulum) analogous to reoxygenation arrhythmias in
intact myocardium, and provided that Cai has not risen above several
micromolar it is returned to resting levels.
We interpret the Cai-independent shortening as a rigor which
activates the myosin ATPase and thereby accelerates ATP depletion so that
ATP-linked ion pumps in the cell membranes become thermodynamically
limited. An ensuing Nai rise
leads through depressed Na-Ca exchange to a Cai rise. Such a model highlights rigor-complex
mediated activation of myosin S1-ATPase as the fundamental target for
interventions to ameliorate ischemic damage to the myocardium.