Dynamic calcium requirements for activation of human ventricular muscle calculated from tension-independent heat

The heat and tension generated by strips of human left ventricle taken from nonfailing hearts were measured at 30 C before and after partial inhibition of ATP splitting by the contractile proteins. We used 2, 3-butanedione monoxime (BDM) (4mM) as the chemical inhibition agent and alterations in solution calcium concentration and stimulus frequency to estimate the heat associated with calcium cycling for a wide range of activation levels. Tension-independent heat (TIH) was used to calculate the total calcium cycled per twitch by assuming that two-thirds of TIH was due to ATP splitting by the sarcoplasmic reticulum CA2+ ATPase with a coupling ratio of 2 Ca2+/ATP split and that one-third of TIH was due to ATP splitting by the sarcolemmal Na+ -K+ ATPase supporting the Na+ -Ca2+ exchanger (1 Ca2+/ATP). The enthalpy of creatine phosphate hydrolysis buffering ATP was taken as -34 KJ/mol. There was a highly positive correlation between TIH and mechanical activation during steady-state and nonsteady-state stimulation. The estimated total calcium turnover per twitch at 39% activation (0.3 Hz pacing rate and 2.5 mM Calcium) was approximately 0.17 nmol/g wet weight. This estimate is less than that calculated from biochemical data describing the cellular content and Ca2+ affinity of major Ca2+ buffers, but is similar to values calculated from recent electron probe microanalysis experiments.