Reduction of extracellular Na+ causes a release of Ca2+ from internal stores in airway epithelial cells.

Exchange of physiological salt solution with Na(+)-free solution caused an increase in intracellular Ca2+ concentration ([Ca2+]i) in 86.3% of cultured airway epithelial cells within 75 s. [Ca2+]i returned to near baseline levels within 45 s and frequently showed oscillatory increases thereafter. When extracellular Na+ concentration ([Na+]o) was reduced to 10 and 60 mM, 59.0 and 8.0% of the cells increased [Ca2+]i, respectively. Low [Na+]o-induced increase in [Ca2+]i was not blocked by amiloride, benzamil, La3+, or the absence of extracellular Ca2+. Low [Na+]o-induced [Ca2+]i increase did not occur after thapsigargin treatment. These results indicated that low [Na+]o-induced [Ca2+]i increase is due to release of Ca2+ from intracellular stores. Because mechanical stimulation of a single cell causes a Ca2+ increase among many cells (Sanderson, M. J., A. C. Charles, and E. R. Dirksen. Mechanical stimulation and intercellular communication increases intracellular Ca2+ in epithelial cells. Cell Regul. 1: 585-596, 1990.) we assayed the effect of low [Na+]o on this mechanically induced response. In low [Na+]o, mechanically induced [Ca2+]i increase in the stimulated cell was reduced; however, [Ca2+]i increase in adjacent cells was normal. We suggest that a mechanically induced Na+ conductance in the stimulated cell contributes to [Ca2+]i changes. These signaling pathways may be involved in the maintenance of periciliary ion concentrations.