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

yExchange 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.