The regulation of calcium cycling in stressed hearts

Myothermal measurements of tension-independent heat are used to calculate the quantity of calcium released during isometric contraction and the rate at which it is removed in control, thyrotoxic and pressure-overloaded rabbit hearts. Experiments were carried out at 30 degrees C. In control rabbit hearts 41.0 +/- 7.0 nmoles/g Ca++ was released into the cytosol for each beat, while the rate at which the Ca++ was removed from the cytosol was 24.4 +/- 4.4 nmoles/g sec. In the presence-overloaded preparations, the amount of calcium released and the rate of calcium removal were 41% and 40% of control values. This reduction was correlated with the mRNA levels for the sarcoplasmic reticulum (SR) Ca++ ATPase, phospholamban and the ryanodine receptor. The depression was also correlated with a reduction in SR Ca++ ATPase protein expression. In thyrotoxic hearts compared with controls, with each activation there is an increase in the amount of calcium liberated into the cytosol (39%) and the rate of calcium removal (31%). This increase is correlated with an increase in the mRNA and protein expression for the SR Ca++ ATPase as well as the mRNA for the ryanodine receptor. Calsequestrin mRNA was unchanged in all of the experimental preparations. It is suggested that the alteration in the calcium cycling proteins offers at least a partial explanation for the changes in calcium cycling measured in response to the stresses applied.(ABSTRACT TRUNCATED AT 250 WORDS)