Intracellular calcium oscillations regulate ciliary beat frequency of airway epithelial cells

Abstract

The effect of ATP-induced Ca2+oscillations on ciliary activity was examined in airway epithelial cells by simultaneously measuring the ciliary beat frequency (CBF) and the intracellular Ca2+concentration ([Ca2+]i) near the base of the cilia. Exposure to extracellular ATP (ATPo) induces a rapid and large increase in both [Ca2+]iand CBF, followed by oscillations in [Ca2+]iand a sustained elevation in CBF. After each Ca2+oscillation, the [Ca2+]ireturned to near basal values. By contrast, the CBF remained elevated during these Ca2+oscillations, although each Ca2+oscillation induced small variations in CBF. During Ca2+oscillations, increases in CBF closely followed the rising phase of increases in [Ca2+]i, but declines in CBF lagged behind declines in [Ca2+]i. Higher frequency Ca2+oscillations reduced variations in CBF, producing a stable and sustained elevation in CBF. The maximal CBF was induced by Ca2+oscillations and was 15% greater than the CBF induced by the substantially larger initial [Ca2+]iincrease. These data demonstrate that the rate of CBF is not directly dependent on the absolute [Ca2+]i, but is dependent on the differential changes in [Ca2+]iand suggest that CBF in airway epithelial cells is regulated by frequency-modulated Ca2+signaling.