Signs of endolymphatic hydrops after perilymphatic perfusion of the guineapig cochlea with cholera toxin; a pharmacological model of acute endolymphatic hydrops
Pjfm. Lohuis et al., Signs of endolymphatic hydrops after perilymphatic perfusion of the guineapig cochlea with cholera toxin; a pharmacological model of acute endolymphatic hydrops, HEARING RES, 137(1-2), 1999, pp. 103-113
There are indications that endolymph homeostasis is controlled by intracell
ular cAMP levels in cells surrounding the scala media. Cholera toxin is a p
otent stimulator of adenylate cyclase, i.e. it increases cAMP levels. We hy
pothesized that perilymphatic perfusion of cholera toxin might increase end
olymph volume by stimulating adenylate cyclase activity, providing us with
a pharmacological model of acute endolymphatic hydrops (EH). Guinea pig coc
hleas were perfused with artificial perilymph (15 min), with or without cho
lera toxin (10 mu g/ml). The endocochlear potential (EP) was measured durin
g and after perfusion. The summating potential (SP), evoked by 2, 4 and 8 k
Hz tone bursts, was measured via an apically placed electrode 0, 1, 2, 3 an
d 4 h after perfusion. Thereafter, the cochleas were fixed to enable measur
ement of the length of Reissner's membrane, reflecting EH. After perfusion
the EP increased significantly over time in the cholera toxin group as comp
ared to the controls. Also, the SP increased gradually at all frequencies i
n the cholera toxin group. Comparison within animals showed that the increa
se in SP became significant after 2 h at 4 kHz, after 3 h at 2 kHz and afte
r 4 h at 8 kHz. In the control group the SP did not change significantly. T
he compound action potential (CAP) amplitude decreased monotonically over t
ime at all frequencies in both the cholera toxin group and the control grou
p, but it decreased faster in the cholera toxin group. Also, the cochlear m
icrophonics amplitude decreased over time at all frequencies in both groups
, but the decrease was significant only in the cholera toxin group after 3
h at 2 and 4 kHz. Quantification of the length of Reissner's membrane showe
d a small but insignificant enlargement in the cholera toxin treated animal
s compared to controls. These results are in accord with our view that EH i
s accompanied by an increase in SP and a decrease in CAP. Our results parti
ally confirm previous results of Feldman and Brusilow (Proc. Natl. Acad. Sc
i. USA (1973) 73, 1761-1764). New aspects in relation to that study are the
significantly increased EP and SP. In the classical EH model, based on obs
truction of the absorptive function of the endolymphatic sac, increased SPs
are accompanied by decreased EPs. In this cholera toxin model of EH, it is
unlikely that the endolymphatic sac is involved. Apparently, EH can be bas
ed on mechanisms located in the cochlea itself as opposed to mechanisms loc
ated in the endolymphatic sac. (C) 1999 Elsevier Science B.V. All rights re
served.