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

Suadicani, Sylvia O., Monique J. Vink, and David C. Spray. Slow intercellular Ca signaling in wild-type and Cx43-null neonatal mouse cardiac myocytes. Am J Physiol Heart Circ Physiol 279: H3076–H3088, 2000.—Focal mechanical stimulation of single neonatal mouse cardiac myocytes in culture induced intercellular Ca waves that propagated with mean velocities of ;14 mm/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 Ca waves, although the velocity and number of cells communicated by the Ca 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 Ca 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 Ca signals in wildtype neonatal mouse cardiac myocytes. Activation of P2receptors induced by ATP release contributes a secondary, extracellular pathway for transmission of Ca signals. The importance of such ATP-mediated Ca signaling would be expected to be enhanced under ischemic conditions, when release of ATP is increased and gap junction channels conductance is significantly reduced.