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

Abstract

Study objective – The plateau of the action potential in heart muscle is largely due to the inward Ca²⁺ current, i_ca; however, Ca²⁺ extrusion via Na⁺/Ca²⁺ exchange may also generate a significant current, i_na/ca. The aim was to assess the influence of i_na/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 i_ca 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 i_ca 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 i_na/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 i_ca, whereas i_na/ca is relatively more important during the later part, and tends to lengthen the action potential.