The Journal of Neuroscience, September 1, 1998, 18(17):6748-6756
Evidence for Opening of Hair-Cell Transducer Channels after
Tip-Link Loss
Jens
Meyer1,
David N.
Furness2,
Hans-Peter
Zenner1,
Carole M.
Hackney2, and
Anthony W.
Gummer1
1 Department of Otolaryngology, Section of
Physiological Acoustics and Communication, University of
Tübingen, 72076 Tübingen, Germany, and
2 Department of Communication and Neuroscience, Keele
University, Keele, Staffordshire ST5 5BG, United Kingdom
The mechanosensitive transducer channels of hair cells have long
been proposed to be gated directly by tension in the tip links. These
are thin, elastic extracellular elements connecting the tips of
adjacent stereocilia located on the apical surface of the cell. If this
hypothesis is true, the channels should close after destruction of tip
links. The hypothesis was tested pharmacologically using receptor
currents obtained in response to mechanical stimulation of the
stereociliary bundle of outer hair cells isolated from the adult guinea
pig cochlea. Application of elastase (20 U/ml) or
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic
acid (BAPTA; 5 mM), both of which are known to
disrupt tip links in other hair-cell preparations, led to the expected
irreversible loss of receptor currents. However, the cells then
displayed a maintained inward current, implying that channels were left
permanently open. This current was similar in magnitude to the receptor
current before treatment and was reduced reversibly by known blockers
of mechanosensitive channels, namely, dihydrostreptomycin (100 µM), amiloride (300 µM), and gadolinium
ions (1 mM). These observations suggest that the maintained
current flows through the mechanosensitive channels. Electron
microscopical analysis of isolated hair cells, exposed to the same
concentrations of elastase or BAPTA as in the electrophysiological experiments, demonstrated an almost total loss of tip links in hair
bundles that showed no evidence of other mechanical damage. It is
concluded that although the tip links are required for
mechanoelectrical transduction, the channels are not gated directly by
the tip links.
Key words:
mechanoelectrical transduction; outer hair cells; tip
link; elastase; low calcium; channel gating; tip-link hypothesis; BAPTA
Copyright © 1998 Society for Neuroscience 0270-6474/98/18176748-09$05.00/0
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