Calcium regulation of ciliary beat frequency in human respiratory epithelium in vitro.
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 less than 0.01) rise in CBF. The increment in CBF was statistically significant 10 min after challenge (+10%; P less than 0.01) and was sustained for at least 1 h, with maximal stimulation after 40 min (+ 18%; P less than 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 less than 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.
Di Benedetto
G
G
Department of Medicine, Faculty of Clinical Sciences, University College, London.
Magnus
C J
CJ
Gray
P T
PT
Mehta
A
A
D000293:Adolescent; D000328:Adult; D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000502:physiology*; D002923:Cilia / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000737:chemistry / Q000502:physiology*; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology
D014268:Trifluoperazine; D000001:Calcimycin; C033170:4-bromo-A-23187; D002118:Calcium