Changing activation sequence in the embryonic chick heart. Implications for the development of the His-Purkinje system

Abstract

In the mature heart, impulse propagation through the His-Purkinje system (HPS) is required for efficient ventricular contraction in an apex-to-base direction. However, the embryonic heart begins to contract as a myocardial tube without a specialized conduction system. To identify the developmental stage when the HPS begins to function, we mapped the ventricular depolarization sequence from microvolt-level electrograms recorded from embryonic myocardium using 50-micron extracellular electrodes, high-gain amplification, and signal-processing techniques. Analysis of left ventricular activation in 99 embryonic hearts revealed a transition in the activation sequence that was dependent on developmental stage. As the heart develops, a transition in the activation sequence occurred from the primitive base-to-apex pattern (in 20 of 33 hearts) at early stages (Hamburger-Hamilton stages 25 to 28) to the HPS-like apex-to-base pattern (12 of 17 hearts) late in development (stages 33 to 36). Immunohistological experiments (n = 10) also confirm that the expression pattern of two biochemical HPS markers changes in parallel with the change to the mature ventricular activation pattern. These data indicate that the ventricular activation sequence in the chick heart develops to a mature pattern at stages 29 to 31, suggesting that preferential conduction through the HPS begins shortly after ventricular septation is complete.