Aminoglycoside antibiotics impair calcium entry but not viability and motility in isolated cochlear outer hair cells.
J. Neurosci. Res.. 1989-10-01; 24(2): 338-346
DOI: 10.1002/jnr.490240226
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1. J Neurosci Res. 1989 Oct;24(2):338-46.
Aminoglycoside antibiotics impair calcium entry but not viability and motility in
isolated cochlear outer hair cells.
Dulon D(1), Zajic G, Aran JM, Schacht J.
Author information:
(1)Kresge Hearing Research Institute, University of Michigan, Ann Arbor
48109-0506.
Cochlear outer hair cells have been well established as primary targets of the
ototoxic actions of aminoglycoside antibiotics. These cells, isolated from the
guinea pig cochlea and maintained in short-term culture, were used as a model for
evaluating the acute effects of gentamicin on cell viability,
depolarization-induced transmembrane calcium flux, and depolarization-induced
motile responses. On the basis of morphology and fluorochromasia, the presence of
extracellular gentamicin as high as 5 mM did not affect the viability of the
cells for up to 6 hr, the longest time tested. Viable cells showed binding of
fluorescently tagged gentamicin to their base but excluded the drug from their
cytoplasm. In response to [K+]-depolarization, intracellular calcium levels
(monitored with the fluorescent calcium-sensitive dye fluo-3) increased from a
resting value of 218 +/- 102 nM to 2,018 +/- 1,077 nM concomitant with a cell
shortening of 0.7% +/- 1.3%. The depolarization-induced calcium increase was
apparently caused by calcium entry into the cell as it was inhibited by the
calcium-channel blocker methoxyverapamil and prevented in the absence of
extracellular calcium. Both gentamicin and neomycin blocked the [K+]-induced
calcium increase at an IC50 of 50 microM. Despite the inhibition of calcium entry
the ability of the outer hair cells to shorten under [K+]-depolarization was not
impaired; in fact, cell shortening was even more pronounced in the absence of
calcium influx (2.6% +/- 1.4%). This argues effectively against the existence of
a calcium-dependent actomyosin-mediated component in [K+]-induced shape
changes.(ABSTRACT TRUNCATED AT 250 WORDS)
DOI: 10.1002/jnr.490240226
PMID: 2585554 [Indexed for MEDLINE]