Intercellular Propagation of Calcium Waves Mediated by Inositol Trisphosphate

Two types of calcium (Ca$^{2+}$) signaling-propagating intercellular Ca$^{2+}$ waves of increasing intracellular Ca$^{2+}$ concentration ([Ca$^{2+}$]$_i$) and nonpropagating oscillations in [Ca$^{2+}$]$_i$-co-exist in a variety of cell types. To investigate this difference in Ca$^{2+}$ signaling, airway epithelial cells were loaded with heparin, an inositol 1,4,5-trisphosphate (IP$_3$) receptor antagonist, by pulsed, high-frequency electroporation. Heparin inhibited propagation of intercellular Ca$^{2+}$ waves but not oscillations of [Ca$^{2+}$]$_i$. In heparin-free cells, Ca$^{2+}$ waves propagated through cells displaying [Ca$^{2+}$]$_i$ oscillations. Depletion of intracellular Ca$^{2+}$ pools with the Ca$^{2+}$-pump inhibitor thapsigargin also inhibited the propagation of Ca$^{2+}$ waves. These studies demonstrate that the release of Ca$^{2+}$ by IP$_3$ is necessary for the propagation of intercellular Ca$^{2+}$ waves and suggest that IP$_3$ moves through gap junctions to communicate intercellular Ca$^{2+}$ waves.