Slow intercellular Ca²⁺ signaling in wild-type and Cx43-null neonatal mouse cardiac myocytes

Focal mechanical stimulation of single neonatal mouse cardiac myocytes in culture induced intercellular Ca²⁺ waves that propagated with mean velocities of ~14 μm/s, reaching ~80% of the cells in the field. Deletion of connexin43 (Cx43), the main cardiac gap junction channel protein, did not prevent communication of mechanically induced Ca²⁺ waves, although the velocity and number of cells communicated by the Ca²⁺ signal were significantly reduced. Similar effects were observed in wild-type cardiac myocytes treated with heptanol, a gap junction channel blocker. Fewer cells were involved in intercellular Ca²⁺ signaling in both wild-type and Cx43-null cultures in the presence of suramin, a P₂-receptor blocker; blockage was more effective in Cx43-null than in wild-type cells. Thus gap junction channels provide the main pathway for communication of slow intercellular Ca²⁺ signals in wild-type neonatal mouse cardiac myocytes. Activation of P₂-receptors induced by ATP release contributes a secondary, extracellular pathway for transmission of Ca²⁺ signals. The importance of such ATP-mediated Ca²⁺ signaling would be expected to be enhanced under ischemic conditions, when release of ATP is increased and gap junction channels conductance is significantly reduced.