Endolymphatic perfusion with EGTA-acetoxymethyl ester inhibits asphyxia- and furosemide-induced decrease in endocochlear potential in guinea pigs.
We examined the effect of the Ca(2+) concentration in the endolymph ([Ca](e)) or in the endolymphatic surface cells ([Ca](i)) on the endocochlear potential (EP) by using an endolymphatic or perilymphatic perfusion technique, respectively. (i) A large increase in [Ca](e) up to approximately 10(-3) M with a fall in the EP was induced by transient asphyxia ( approximately 2 min) or by the intravenous administration of furosemide (60 mg/kg), and a significant correlation was obtained between the EP and p[Ca](e) (= -log [Ca](e), r = 0.998). (ii) Perfusion of the endolymph with 10 mM EGTA for 5 min neither produced any significant change in the EP nor altered the asphyxia-induced change in EP (DeltaEP(asp)), suggesting that neither [Ca](e) nor the Ca(2+) concentration gradient across the stria vascularis contributed directly to the generation of the EP in the condition of low [Ca](e). In contrast, endolymphatic perfusion with high Ca(2+) (more than 10 mM) produced a decrease in EP and a significant correlation was obtained between the EP and the Ca(2+) concentration of perfusion solution (r = 0.982), suggesting that Ca(2+) permeability may exist across the stria vascularis. (iii) The administration of a Ca(2+) chelator, EGTA-acetoxymethyl ester (AM, 0.3 mM), to the endolymph, which produced a gradual increase in EP, suppressed significantly, by 60-80%, DeltaEP(asp) or furosemide-induced changes in EP. In contrast, perilymphatic administration of 0.5 mM EGTA-AM caused no significant suppression of the DeltaEP(asp). These findings suggest that [Ca](i) plays an important role in generating/maintaining a large positive EP.
Mineharu
Akihito
A
Department of Physiology II and Department of Otolaryngology, Osaka Medical College, Takatsuki, Osaka, 569-8686 Japan.
Mori
Yoshiaki
Y
Nimura
Yoshitsugu
Y
Takamaki
Atsuko
A
Araki
Michitoshi
M
Yamaji
Junko
J
Yoshida
Ryotaro
R
Takenaka
Hiroshi
H
Kubota
Takahiro
T
D000818:Animals; D001237:Asphyxia / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003051:Cochlea / Q000502:physiology*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects* / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004710:Endolymph / Q000187:drug effects / Q000502:physiology*; D005665:Furosemide / Q000494:pharmacology; D006168:Guinea Pigs; D008839:Microelectrodes; D010477:Perfusion; D010498:Perilymph / Q000187:drug effects / Q000502:physiology
D002614:Chelating Agents; D004232:Diuretics; D004533:Egtazic Acid; D005665:Furosemide; C046770:EGTA acetoxymethyl ester; D002118:Calcium