Effects of Nitrogen Mustard-N-Oxide on Ionic Activities of Inner Ear Fluid and Ionic Permeabilities of the Cochlear Partition in the Guinea Pig

Abstract

The effect of nitrogen mustard-N-oxide (NMO) on the endocochlear potential (EP) was investigated from the aspect of the ion concentrations and permeabilities in the cochlea. Compared with the untreated animals, in NMO-treated animals 20 to 30 hours after administration, the EP was decreased (30.8 ± 3.5 mV in NMO versus 82.4 ± 1.6 mV in control), the K⁺ concentration in perilymph of the scala tympani was increased (8.2 ± 1.0 mM versus 5.3 ± 0.7 mM), the K⁺ concentration in endolymph was decreased (128.5 ± 10.6 mM versus 157.9 ± 7.9 mM), and the Na⁺ concentration in endolymph was increased (9.6 ± 3.6 mM versus 2.5 ± 0.4 mM). The permeability coefficient for Na⁺ of the cochlear partition in the NMO-treated animals significantly decreased, while that for Cl⁻ significantly increased. The negative EP, which presumably exists in the normal state, diminished further (−2.7 mV versus −27.8 mV), and the calculated electrogenic potential of the EP was depressed remarkably (33.5 mV versus 110.2 mV). The results suggest that the effects of NMO involved changes in ion permeabilities of the partition and the inhibition of electrogenic transport processes in the cochlea.

Keywords

anoxia electrogenic potential endocochlear potential

Get full access to this article

View all access options for this article.

References

Cummings

. Experimental observations on the ototoxicity of nitrogen mustard. Laryngoscope 1968; 78: 530–8.

Nakai

. Ototoxic effect of nitromin and some congenital deaf animal cochlea. An electron microscopical study. Arch Otorhinolaryngol 1971; 198: 325–38.

Asakuma

Yoshida

Toriya

Hirashima

. Experimental study of the mechanism of the decrease in endocochlear d.c. potential after administration of nitrogen mustard-N-oxide. Acta Otolaryngol (Stockh) 1984; 97: 273–82.

Ikeda

Kusakari

Kawamoto

. N₁ latency prolongation in the guinea pig cochlea treated with nitrogen mustard-N-oxide studied by narrow band analysis. Ann Otol Rhinol Laryngol 1987; 96: 182–6.

Konishi

Kelsey

Singleton

. Negative potential in scala media during early stage of anoxia. Acta Otolaryngol (Stockh) 1967; 64: 107–18.

Asakuma

Lowry

Snow

Jr. . Effect of kanamycin sulfate on the endocochlear dc potential in guinea pigs. Arch Otolaryngol 1979; 105: 145–8.

Ikeda

Kusakari

Takasaka

. The effect of the cationic composition in perilymph upon the N₁ latency of the guinea pig. Acta Otolaryngol (Stockh) 1987; 103: 43–9.

Ikeda

Kusakari

Takasaka

Saito

. The Ca²⁺ activity of cochlear endolymph of the guinea pig and the effect of inhibitors. Hear Res 1987; 26: 117–25.

Saito

Ozawa

Hayashi

Nishiyama

. Acetylcholine-induced change in intracellular Cl⁻ activity of the mouse lacrimal acinar cells. Pflügers Arch 1985; 405: 108–11.

10.

Lee

. Ionic activities in cardiac muscle cells and application of ion-selective microelectrodes. Am J Physiol 1981; 241: H459–78.

11.

Konishi

Salt

. Permeability to potassium of the endolymph-perilymph barrier and its possible relation to hair cell function. Exp Brain Res 1980; 40: 457–63.

12.

Mori

Konishi

. Permeability to chloride ions of the cochlear partition in normal guinea pigs. Hear Res 1985; 17: 227–36.

13.

Konishi

Mori

. Permeability to sodium ions of the endolymph-perilymph barrier. Hear Res 1984; 15: 143–9.

14.

Johnstone

. The relation between endolymph and the endocochlear potential during anoxia. Acta Otolaryngol (Stockh) 1965; 60: 113–20.

15.

Kuijpers

Bonting

. The cochlear potentials II. The nature of the cochlear endolymphatic resting potential. Pflügers Arch 1970; 320: 359–72.

16.

Konishi

. Some observations on negative endocochlear potential during anoxia. Acta Otolaryngol (Stockh) 1979; 87: 506–16.

17.

Bosher

. The nature of the negative endocochlear potentials produced by anoxia and ethacrynic acid in the rat and guinea-pig. J Physiol (Lond) 1979; 293: 329–45.

18.

Kusakari

Rokugo

Kambayashi

. Generation mechanism of the negative endocochlear potential during early stage of anoxia. ORL 1983; 45: 195–202.

19.

Marcus

Rokugo

X-X

Thalmann

. Response of cochlear potentials to presumed alterations of ionic conductance: Endolymphatic perfusion of barium, valinomycin and nystatin. Hear Res 1983; 12: 17–30.

20.

Marcus

. Characterization of potassium permeability of cochlear duct by perilymphatic perfusion of barium. Am J Physiol 1984; 247: C240–6.

21.

Komune

Huangfu

Snow

Jr. . A possible site of production of the negative endocochlear dc potential. Hear Res 1985; 18: 153–8.

22.

Melichar

Syka

. Electrophysiological measurement of the stria vascularis potentials in vivo. Hear Res 1987; 25: 35–43.

23.

Baxter

Chahwala

Hickman

Spurgin

. The effects of nitrogen mustard (NH₂) on activities of plasma membrane of PC6A mouse plasmacytoma cells. Biochem Pharmacol 1982; 31: 1773–8.

24.

Doppler

Hofmann

Oberhuber

Maly

Grunicke

. Nitrogen mustard interference with potassium transport systems in Ehrlich ascites tumor cells. J Cancer Res Clin Oncol 1985; 110: 35–41.

25.

Sellick

Johnstone

. Production and role of inner ear fluid. Prog Neurobiol 1975; 5: 337–62.

26.

Offner

Dallos

Cheatham

. Positive endocochlear potential: Mechanism of production by marginal cells of stria vascularis. Hear Res 1987; 29: 117–24.

27.

Salt

Melichar

Thalmann

. Mechanisms of endocochlear potential generation by stria vascularis. Laryngoscope 1987; 87: 984–91.

28.

Bosher

. The effects of inhibition of the strial Na⁺-K⁺-activated ATPase by perilymphatic ouabain in the guinea pig. Acta Otolaryngol (Stockh) 1980; 90: 219–29.