Intracellular Ca²⁺ Oscillations, a Potential Pacemaking Mechanism in Early Embryonic Heart Cells

Early (E9.5–E11.5) embryonic heart cells beat spontaneously, even though the adult pacemaking mechanisms are not yet fully established. Here we show that in isolated murine early embryonic cardiomyocytes periodic oscillations of cytosolic Ca²⁺ occur and that these induce contractions. The Ca²⁺ oscillations originate from the sarcoplasmic reticulum and are dependent on the IP₃ and the ryanodine receptor. The Ca²⁺ oscillations activate the Na⁺-Ca²⁺ exchanger, giving rise to subthreshold depolarizations of the membrane potential and/or action potentials. Although early embryonic heart cells are voltage-independent Ca²⁺ oscillators, the generation of action potentials provides synchronization of the electrical and mechanical signals. Thus, Ca²⁺ oscillations pace early embryonic heart cells and the ensuing activation of the Na⁺-Ca²⁺ exchanger evokes small membrane depolarizations or action potentials.