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Intracellular pathways regulating ciliary beating of rat brain ependymal cells
Author(s) -
Nguyen Thien,
Chin WeiChun,
O'Brien Jennifer A.,
Verdugo Pedro,
Berger Albert J.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0131j.x
Subject(s) - extracellular , ependymal cell , intracellular , cytosol , slice preparation , biophysics , chemistry , brainstem , biology , medicine , endocrinology , microbiology and biotechnology , neuroscience , central nervous system , biochemistry , enzyme
1 The mammalian brain ventricles are lined with ciliated ependymal cells. As yet little is known about the mechanisms by which neurotransmitters regulate cilia beat frequency (CBF). 2 Application of 5‐HT to ependymal cells in cultured rat brainstem slices caused CBF to increase. 5‐HT had an EC 50 of 30 μM and at 100 μM attained a near‐maximal CBF increase of 52.7 ± 4.1 % (mean ± s.d.) ( n = 8 ). 3 Bathing slices in Ca 2+ ‐free solution markedly reduced the 5‐HT‐mediated increase in CBF. Fluorescence measurements revealed that 5‐HT caused a marked transient elevation in cytosolic Ca 2+ ([Ca 2+ ] c ) that then slowly decreased to a plateau level. Analysis showed that the [Ca 2+ ] c transient was due to release of Ca 2+ from inositol 1,4,5‐trisphosphate (IP 3 )‐sensitive stores; the plateau was probably due to extracellular Ca 2+ influx through Ca 2+ release‐activated Ca 2+ (CRAC) channels. 4 Application of ATP caused a sustained decrease in CBF. ATP had an EC 50 of about 50 μM and 100 μM ATP resulted in a maximal 57.5 ± 6.5 % ( n = 12 ) decrease in CBF. The ATP‐induced decrease in CBF was unaffected by lowering extracellular [Ca 2+ ], and no changes in [Ca 2+ ] c were observed. Exposure of ependymal cells to forskolin caused a decrease in CBF. Ciliated ependymal cells loaded with caged cAMP exhibited a 54.3 ± 7.5 % ( n = 9 ) decrease in CBF following uncaging. These results suggest that ATP reduces CBF by a Ca 2+ ‐independent cAMP‐mediated pathway. 5 Application of 5‐HT and adenosine‐5′‐ O ‐3‐thiotriphosphate (ATP‐γ‐S) to acutely isolated ciliated ependymal cells resulted in CBF responses similar to those of ependymal cells in cultured slices suggesting that these neurotransmitters act directly on these cells. 6 The opposite response of ciliated ependymal cells to 5‐HT and ATP provides a novel mechanism for their active involvement in central nervous system signalling.