Intercellular Propagation of Calcium Waves Mediated by Inositol Trisphosphate

TLDR

Two types of calcium signaling—propagating intercellular Ca²⁺ waves and nonpropagating oscillations—co‑exist in various cell types. To investigate the difference in Ca²⁺ signaling between propagating waves and nonpropagating oscillations. Airway epithelial cells were loaded with the IP₃ receptor antagonist heparin via pulsed, high‑frequency electroporation. Heparin blocked intercellular Ca²⁺ wave propagation without affecting oscillations, and depletion of intracellular Ca²⁺ stores with thapsigargin similarly inhibited wave spread, demonstrating that IP₃‑mediated Ca²⁺ release is essential for wave propagation and likely travels through gap junctions to coordinate intercellular signaling.

Abstract

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.