Changes in intracellular Ca2+ activity with stimulation in sheep cardiac Purkinje strands

One hypothesis to explain increased contraction strength with increased stimulation rate in heart muscle requires that stimulation increase intracellular Na+ activity(aiNa). This is proposed to increase intracellular Ca2+ activity (aiCa) via the Na-Ca exchange mechanism. Several indirect studies have supported the idea that aiNa is increased with stimulation, and more recently we have directly demonstrated aiNa elevation with Na+-sensitive microelectrodes. We now report aiCa to be elevated after trains of stimuli at different rates in sheep cardiac Purkinje strands. The resting level of aiCa in six strands was 93 +/- 15 (SE) nM, and it increased to 162 +/- 20 nM after stimulation at 3 Hz. The recovery of aiCa was exponential, and the time constants of 80-120 s were similar to those previously found for aiNa. A positive force-frequency relation was found in sheep Purkinje fibers that correlated with the increased aiCa. The results support the hypothesis that the Na-Ca exchange system plays an important role in the force-frequency phenomenon.