Ca²⁺ Transients in Perfused Hearts: Fundamental Properties of the Chemical Signals Underlying Ventricular Mechanics

Summary

An increase in the intracellular free calcium concentration, [Ca²⁺]_i, initiates contractile activation in the heart. Until recently, the changes in [Ca²⁺]_i during the cardiac cycle (the “Ca²⁺ transients”) had eluded measurement. Here I describe the use of gated nuclear magnetic resonance (NMR) spectroscopy to achieve direct quantitation of the cyclical changes in [Ca²⁺]_i that underlie mechanics in perfused ferret hearts loaded with-the fluorinated Ca²⁺ indicator 5F-BAPTA. [Ca²⁺]_i increased from approximately 200 nM in diastole to 750 nM or higher in early systole. In this preparation, the effects of changing coronary arterial flow on [Ca²⁺]_i can be investigated simultaneously with measurements of high-energy phosphate concentrations by ³¹P-NMR. When hypoperfusion is induced such that the pressure generated by contraction falls without metabolic evidence of ischemia (“Gregg’s phenomenon”), a decrease in the amplitude of Ca²⁺ transients underlies the observed fall in pressure. This down-regulation of Ca²⁺ transients constitutes the cellular basis for Gregg’s phenomenon, and serves to decrease energy demand during low-flow ischemia.