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Effect of intravenous aminooxyacetic acid on guinea pig cochlear potentials
Neuropharmacology,
1973.
12, 1005-1007
PergamonPress. Printedin 13. Britain.
EFFECT OF INTRAVENOUS AMINOOXYACETIC ACID ON GUINEA PIG COCHLEAR POTENTIALS* R. P. BOBBIN? and M. GONDRA Kresge Hearing Research Laboratory, Department of Otorhinolaryngology, Louisiana State University School of Medicine, New Orleans, Louisiana 70119 (Accepted
5 May 1973)
Summary-Aminooxyacetic acid (AOAA) injected intravenously in doses of 10-80 mg/kg into anaesthetized and paralyzed guinea pigs produced a reduction in the endocochlear potential, the cochlear microphonics and the compound action potential of cochlear nerve. The reduction in the potentials reached a maximum approximately 1 hr after injection. At present, the mechanism for this action is unknown.
BOBBIN, GONZALES and GUTH (1969) first suggested that aminooxyacetic acid (AOAA) produced a change in the hearing mechanism. They reported a reversible increase in the hearing threshold of guinea pigs after administration of AOAA. An effect on the cochlea was demonstrated when it was shown that the agent decreased the compound action potential of the cochlear nerve (BOBBIN and GUTH, 1970). The present study was performed to elucidate further the actions of AOAA on the cochlear potentials.
METHODS
Guinea pigs anaesthetized with pentobarbital and paralyzed with gallamine were used. Rectal temperature was maintained at 36-38°C. Recordings of the compound action potential of the cochlear nerve and the cochlear microphonics in response to 6 kHz tone bursts were obtained from the basal turn by the differential electrode technique (TASAKI, DAVIS and LEGOUIX, 1952). The sound pressure level (SPL) was measured in decibels (dB) above the reference of 04002 dyn/cm2. The endocochlear potential was recorded by a microelectrode inserted in the Scala media through the spiral ligament of the basal turn. The right jugular vein was cannulated for drug administration and the right carotid artery was cannulated for monitoring blood pressure. RESULTS
The blood pressure was lowered by the injection of AOAA. However, when the blood pressure was lowered to a greater degree by pentobarbital no change in the cochlear potentials was observed. At a dose of 80 mg/kg, AOAA appeared to induce cardiac arrhythmias * This investigation was supported by a grant from The Deafness Research Foundation and the Louisiana State University General Research Support Fund. Necessary laboratory facilities were provided through a grant from The Kresge Foundation. t Also Department of Pharmacology. 1005
R. P. BOBBIN and M. GONDRA
1006
and failure approximately 1 hr after injection in three out of five animals. Thus, data presented at the 80 mg/kg dose are for two animals only. The change in the endocochlear potential observed in the control animals was totally accounted for by the drift in the endocochlear potential recording system (Fig. 1). The drift
1
151 w e--t
w
(51
Conlrols 10mgikg
-
20 mgikg
w
40mgikg
r-x
80 mgikg
. ._.d-._.*-.
I
-lOj_ 0
10‘I
20
r
30
40 Time
r
50 after
”
f
60
AOAA
70
80
90
loo
110
r
in Minutes
Fig. 1. Effect of AOAA on the endocochlear potential. Each point represents the mean of the number of animals indicated within brackets. Vertical bars: range at 60 min. for all animals ranged from + 3 to - 8 mV per hour. The results shown in Figure 1 were not corrected for this drift. Injection of AOAA in doses of 10-80 mg/kg, i.v., decreased the endocochlear potential in a dose-response manner (Fig. 1). The maximum reduction occurred 4C65 min after injection. Recovery commenced rapidly after the endocochlear potential reached its maximum reduction (Fig. 1). In three animals a 90% recovery of the endocochlear potential (drift corrected) was observed 5 hr after the injection of 40 mg/kg of AOAA. The magnitude of the cochlear microphonics and the compound action potential of the cochlear nerve were reduced by AOAA (lo-80 mg/kg, i.v.) in parallel with the endocochlear potential. The effect of AOAA (40 mg/kg, i.v.) on these potentials at the time of maximum reduction in the endocochlear potential is illustrated in Figure 2. DISCUSSION The source of the endocochlear potential has been demonstrated to be in the stria vascularis (TASAKI and SPYROPOULOS, 1959). Since AOAA reduced the magnitude of this potential it appears that one of the sites of action of AOAA is in the stria vascularis. The magnitude of both the cochlear microphonics and the action potential have been shown to be dependent on the magnitude of the endocochlear potential (HONRUBIA and WARD, 1969; KONISHI and MENDELSOHN, 1970). Thus the reduction in these potentials observed after the administration of AOAA was probably due to the reduction in the endocochlear potential.
Aminooxyacetic
1007
acid
Aminooxyacetic acid has been shown to inhibit vitamin Be-dependent enzymes (HOTTA, 1968;HOTTAand LEVINSON, 1970). However, at present, we have no evidence that AOAA has any action on a vitamin B,-dependent enzyme in the cochlea. PV
Cochlea
MIcrophonics
Action
PV
Potential
5Oxl i
Attenuation in dB
Fig. 2. Effect of AOAA (40 mg/kg, i.v.) on the compound action potential of the cochlear nerve and the cochlear microphonics elicited by the 6 kHz tone burst. Means and ranges from five aninials are given. The curves were obtained before and 54-78 min after injection. OdB attenuation = 129 dB SPL. authors express thanks to C. Dr. C. I. BERLINand J. K. CULLEN,JR., for consultation.
Acknowledgements-The
WIESENDANGER
for technical
assistance
and to
REFERENCES BOBBIN,R. P., GONZALES,G. and GUTH, P. S. (1969). Effects of aminooxyacetic acid on cochlear potentials and the Preyer reflex. Nature, Lond. 223: 70-71. BOBBIN,R. P. and GUTH, P. S. (1970). Evidence that gamma-aminobutyric acid is not the inhibitory transmitter at the crossed olivocochlear nerve-hair cell junction. Neuropharmacology 9: 567-574. HONRUBIA,V. and WARD, P. H. (1969). Dependence of the cochlear microphonics and the summating potential on the endocochlear potential. J. acoust. Sot. Am. 46: 388-392. HOTTA, S. S. (1968). Oxidative metabolism of isolated brain mitochondria: changes caused by aminooxyacetate. Archs Biochem. Biophys. 127: 132-139. HOTTA, S. S. and LEVINSON,B. S. (1970). The effects of aminooxyacetate on the metabolism of glucose and glutamate by homogenates of guinea pig cerebral hemispheres. Tax. appl. Pharmac. 16: 154-165. KONISHI,T. and MENDELSOHN, M. (1970). Effect of Ouabain on cochlear potentials and endolymph composition in guinea pigs. Acta oto lar. 69: 192-199. TASAKI,I., DAVIS,H. and LEGOUIX,I. P. (1952). The space time pattern of the cochlear microphonics (guinea pigs) as recorded by differential electrodes. J. acoust. Sot. Am. 45: 502-519. TASAKI, I. and SPYROPOULOS,C. S. (1959). Stria vascularis as source of endocochlear potential. J. Neurophysiol.
22
: 149-155.
1973.
12, 1005-1007
PergamonPress. Printedin 13. Britain.
EFFECT OF INTRAVENOUS AMINOOXYACETIC ACID ON GUINEA PIG COCHLEAR POTENTIALS* R. P. BOBBIN? and M. GONDRA Kresge Hearing Research Laboratory, Department of Otorhinolaryngology, Louisiana State University School of Medicine, New Orleans, Louisiana 70119 (Accepted
5 May 1973)
Summary-Aminooxyacetic acid (AOAA) injected intravenously in doses of 10-80 mg/kg into anaesthetized and paralyzed guinea pigs produced a reduction in the endocochlear potential, the cochlear microphonics and the compound action potential of cochlear nerve. The reduction in the potentials reached a maximum approximately 1 hr after injection. At present, the mechanism for this action is unknown.
BOBBIN, GONZALES and GUTH (1969) first suggested that aminooxyacetic acid (AOAA) produced a change in the hearing mechanism. They reported a reversible increase in the hearing threshold of guinea pigs after administration of AOAA. An effect on the cochlea was demonstrated when it was shown that the agent decreased the compound action potential of the cochlear nerve (BOBBIN and GUTH, 1970). The present study was performed to elucidate further the actions of AOAA on the cochlear potentials.
METHODS
Guinea pigs anaesthetized with pentobarbital and paralyzed with gallamine were used. Rectal temperature was maintained at 36-38°C. Recordings of the compound action potential of the cochlear nerve and the cochlear microphonics in response to 6 kHz tone bursts were obtained from the basal turn by the differential electrode technique (TASAKI, DAVIS and LEGOUIX, 1952). The sound pressure level (SPL) was measured in decibels (dB) above the reference of 04002 dyn/cm2. The endocochlear potential was recorded by a microelectrode inserted in the Scala media through the spiral ligament of the basal turn. The right jugular vein was cannulated for drug administration and the right carotid artery was cannulated for monitoring blood pressure. RESULTS
The blood pressure was lowered by the injection of AOAA. However, when the blood pressure was lowered to a greater degree by pentobarbital no change in the cochlear potentials was observed. At a dose of 80 mg/kg, AOAA appeared to induce cardiac arrhythmias * This investigation was supported by a grant from The Deafness Research Foundation and the Louisiana State University General Research Support Fund. Necessary laboratory facilities were provided through a grant from The Kresge Foundation. t Also Department of Pharmacology. 1005
R. P. BOBBIN and M. GONDRA
1006
and failure approximately 1 hr after injection in three out of five animals. Thus, data presented at the 80 mg/kg dose are for two animals only. The change in the endocochlear potential observed in the control animals was totally accounted for by the drift in the endocochlear potential recording system (Fig. 1). The drift
1
151 w e--t
w
(51
Conlrols 10mgikg
-
20 mgikg
w
40mgikg
r-x
80 mgikg
. ._.d-._.*-.
I
-lOj_ 0
10‘I
20
r
30
40 Time
r
50 after
”
f
60
AOAA
70
80
90
loo
110
r
in Minutes
Fig. 1. Effect of AOAA on the endocochlear potential. Each point represents the mean of the number of animals indicated within brackets. Vertical bars: range at 60 min. for all animals ranged from + 3 to - 8 mV per hour. The results shown in Figure 1 were not corrected for this drift. Injection of AOAA in doses of 10-80 mg/kg, i.v., decreased the endocochlear potential in a dose-response manner (Fig. 1). The maximum reduction occurred 4C65 min after injection. Recovery commenced rapidly after the endocochlear potential reached its maximum reduction (Fig. 1). In three animals a 90% recovery of the endocochlear potential (drift corrected) was observed 5 hr after the injection of 40 mg/kg of AOAA. The magnitude of the cochlear microphonics and the compound action potential of the cochlear nerve were reduced by AOAA (lo-80 mg/kg, i.v.) in parallel with the endocochlear potential. The effect of AOAA (40 mg/kg, i.v.) on these potentials at the time of maximum reduction in the endocochlear potential is illustrated in Figure 2. DISCUSSION The source of the endocochlear potential has been demonstrated to be in the stria vascularis (TASAKI and SPYROPOULOS, 1959). Since AOAA reduced the magnitude of this potential it appears that one of the sites of action of AOAA is in the stria vascularis. The magnitude of both the cochlear microphonics and the action potential have been shown to be dependent on the magnitude of the endocochlear potential (HONRUBIA and WARD, 1969; KONISHI and MENDELSOHN, 1970). Thus the reduction in these potentials observed after the administration of AOAA was probably due to the reduction in the endocochlear potential.
Aminooxyacetic
1007
acid
Aminooxyacetic acid has been shown to inhibit vitamin Be-dependent enzymes (HOTTA, 1968;HOTTAand LEVINSON, 1970). However, at present, we have no evidence that AOAA has any action on a vitamin B,-dependent enzyme in the cochlea. PV
Cochlea
MIcrophonics
Action
PV
Potential
5Oxl i
Attenuation in dB
Fig. 2. Effect of AOAA (40 mg/kg, i.v.) on the compound action potential of the cochlear nerve and the cochlear microphonics elicited by the 6 kHz tone burst. Means and ranges from five aninials are given. The curves were obtained before and 54-78 min after injection. OdB attenuation = 129 dB SPL. authors express thanks to C. Dr. C. I. BERLINand J. K. CULLEN,JR., for consultation.
Acknowledgements-The
WIESENDANGER
for technical
assistance
and to
REFERENCES BOBBIN,R. P., GONZALES,G. and GUTH, P. S. (1969). Effects of aminooxyacetic acid on cochlear potentials and the Preyer reflex. Nature, Lond. 223: 70-71. BOBBIN,R. P. and GUTH, P. S. (1970). Evidence that gamma-aminobutyric acid is not the inhibitory transmitter at the crossed olivocochlear nerve-hair cell junction. Neuropharmacology 9: 567-574. HONRUBIA,V. and WARD, P. H. (1969). Dependence of the cochlear microphonics and the summating potential on the endocochlear potential. J. acoust. Sot. Am. 46: 388-392. HOTTA, S. S. (1968). Oxidative metabolism of isolated brain mitochondria: changes caused by aminooxyacetate. Archs Biochem. Biophys. 127: 132-139. HOTTA, S. S. and LEVINSON,B. S. (1970). The effects of aminooxyacetate on the metabolism of glucose and glutamate by homogenates of guinea pig cerebral hemispheres. Tax. appl. Pharmac. 16: 154-165. KONISHI,T. and MENDELSOHN, M. (1970). Effect of Ouabain on cochlear potentials and endolymph composition in guinea pigs. Acta oto lar. 69: 192-199. TASAKI,I., DAVIS,H. and LEGOUIX,I. P. (1952). The space time pattern of the cochlear microphonics (guinea pigs) as recorded by differential electrodes. J. acoust. Sot. Am. 45: 502-519. TASAKI, I. and SPYROPOULOS,C. S. (1959). Stria vascularis as source of endocochlear potential. J. Neurophysiol.
22
: 149-155.