Influence of electrogenic Na/Ca exchange on the action potential in human heart muscle

Study objective – The plateau of the action potential in heart muscle is largely due to the inward Ca2+ current, ica; however, Ca2+ extrusion via Na+/Ca2+ exchange may also generate a significant current, ina/ca. The aim was to assess the influence of ina/ca on the action potential in isolated human heart muscle. Design – Action potentials and force of isometric contractions were recorded in ventricular trabeculae. The muscle was subjected to various stimulus patterns, Ca2+ antagonists, and variations in the ionic composition of the extracellular medium. Patients – From 49 patients, aged 0.5 to 14 years, small right ventricular trabeculae were obtained during open heart surgery. The operations concerned corrections of ventricular septal defects. Data presented in this paper were from nine preparations in which action potentials were recorded during several hours. Measurements and main results – The results confirmed that: (1) the amplitude of the early part of the plateau was depressed by low [Ca2+] and by Ca2+ antagonists, showing that ica dominates this early part; and (2) that low [Na2+] and post-extrasystolic potentiation also depressed the early component of the plateau of the action potential, which can be explained by inactivation of ica due to increased levels of intracellular Ca2+. A novel observation was that post-extrasystolic potentiation led to an increase in action potential duration (APD). An explanation is that the potentiated contraction follows from an increased amount of intracellular Ca2+ which also activates an inward current, possibly ina/ca. This assumption is strengthened by the finding that lengthening of APD after extrasystoles was abolished: (a) at low [Ca2+], ie, when force was small and there was little Ca2+ to be extruded; and (b) at low [Na+], ie, when force was large but the driving force of the Na+ gradient for extrusion of Ca2+ was small. Conclusions – The early part of the plateau is dominated by ica, whereas ina/ca is relatively more important during the later part, and tends to lengthen the action potential.