Extracellular Na' Concentration Changes Cause Release of Ca3' from Intracellular Stores in Airway Epithelial Cells

The maintenance of ion transport and its subsequent effects on the electrolyte composition of the periciliary layer is an important function of the airway epithelium. Electrolyte movement, including Na absorption, is tightly regulated and involves second messenger regulation. In this report we use digital image microscopy and the Ca2sensitive dye fura-2 to examine intracellular Ca:' changes in response to changes of extracellular Na' concentration ([Na'Jj. Removing [Na ]0 (or reducing [Na ]0 from 138 mM to 10 mM) in cultures of airway cells (by Li' or choline substitution) causes [Ca2'], to increase from resting levels of approx. 50 nM to greater than 400 nM within 30 seconds of changing the Na' solution. [Ca3'], returns to baseline in 45 sec and then displays an oscillatory behavior. When Na is added back to the culture medium, oscillatory patterns of [Ca2], are stopped and [Ca2], returns to resting values. These responses occur in the presence of the Na channel and NaVCa2exchanger blockers amiloride (lOuM) or benzamil (10 -M), and in the absence of [Ca2']. However, if Na' is removed following the emptying of intracellular stores of Ca3' with thapsigargin, no increase in [Ca2], is observed. We conclude that the airway epithelium can respond to changes in [Na']0 by release of Ca2from intracellular stores, and thus, [Ca2], may play an important role in electrolyte movement. Supported by grants from the Tobacco Related Disease Research Council of the Univ. of California and NASA Microgravity Research. S.B. is a Parker B. Francis Fellow in Pulmonary Research.