Intercellular Ca²⁺ signaling in alveolar epithelial cells through gap junctions and by extracellular ATP

Inter- and extracellular-mediated changes in intracellular Ca²⁺ concentration ([Ca²⁺]_i) can ensure coordinated tissue function in the lung. Cultured rat alveolar epithelial cells (AECs) have been shown to respond to secretagogues with increases in [Ca²⁺]_i and have been shown to be gap junctionally coupled. However, communication of [Ca²⁺]_i changes in AECs is not well defined. Monolayers of AECs were mechanically perturbed and monitored for [Ca²⁺]_i changes. Perturbation of AECs was administered by a glass probe to either mechanically stimulate or mechanically wound individual cells. Both approaches induced a change in [Ca²⁺]_i in the stimulated cell that was propagated to neighboring cells (Ca²⁺ waves). A connexin mimetic peptide shown to uncouple gap junctions eliminated Ca²⁺ waves in mechanically stimulated cells but had no effect on mechanically wounded cells. In contrast, apyrase, an enzyme that effectively removes ATP from the extracellular milieu, had no effect on mechanically stimulated cells but severely restricted mechanically wounded Ca²⁺ wave propagation. We conclude that AECs have the ability to communicate coordinated Ca²⁺ changes using both gap junctions and extracellular ATP.