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.