CALCIUM REGULATION OF CILIARY BEAT FREQUENCY IN HUMAN RESPIRATORY EPITHELIUM INVITRO

1. The changes in ciliary beat frequency (CBF) of human nasal respiratory epithelial cells were measured in vitro with a photometric technique following exposure to either 4-bromo-calcium ionophore A23187 (4-Br-A23187) or trifluoperazine (TFP), an inhibitor of calmodulin-sensitive calcium-dependent protein kinases. Changes in intracellular free calcium concentrations in response to 4-Br-A23187 were studied using a fluorescent dye (Fura-2). 2. Addition of 10(-5) M-4-Br-A23187 caused a time-dependent (P < 0.01) rise in CBF. The increment in CBF was statistically significant 10 min after challenge (+10%; P < 0.01) and was sustained for at least 1 h, with maximal stimulation after 40 min (+18%; P < 0.01). 3. Exposure to 10(-5) M-4-Br-A23187 caused an immediate increase in intracellular free calcium concentration, which preceded the rise in CBF. 4. TFP (10(-4) M) caused a reduction of baseline CBF (-10%; P < 0.01) and prevented the expected rise when the cells were subsequently exposed to 10(-5) M-4-Br-A23187. 5. We conclude that: (1) calcium ionophore stimulates the CBF of human respiratory cells; (2) this effect is mediated through a calmodulin-sensitive system, since it is abolished in the presence of TFP; (3) the same pathway appears to control the basal CBF of these cells, since TFP also decreases CBF.