Excitatory amino acid response in isolated spiral ganglion cells of guinea pig cochlea.
1. The physiological and pharmacological properties of excitatory amino acid (EAA)-induced responses were investigated in acutely isolated spiral ganglion cells of guinea pig by a conventional patch-clamp technique combined with a rapid drug application (Y-tube) method. 2. L-glutamate (Glu) and its agonists, quisqualate (QA) and kainate (KA), induced inward currents in a concentration-dependent manner at a holding potential (VH) of -70 mV. The values of half-maximal concentration (EC50) were 4.0 x 10(-4) M for Glu, 2.3 x 10(-5) M for QA, and 1.4 x 10(-4) for KA. The Hill coefficients were 0.96, 1.00, and 1.56 for Glu, QA, and KA, respectively. However, one of Glu agonists, N-methyl-D-aspartate (NMDA), and another excitatory amino acid, L-aspartate (Asp), did not induce any responses even in Mg2(+)-free external solution containing 10(-6) M glycine (Gly). 3. The current-voltage (I-V) relationships for the Glu-, QA-, and KA-induced responses were linear, and these reversal potentials were near 5 mV. 4. Kynurenic acid (Kyn), 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic acid (diCl-HQC), and quinoxalinediones such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX) suppressed the Glu-, QA-, and KA-induced currents in a concentration-dependent manner. The inhibitory potency was in the order of DNQX = CNQX greater than diCl-HQC greater than Kyn. 5. CNQX antagonized the Glu-, QA-, and KA-induced currents without affecting the maximum responses showing no voltage-dependency, indicating the competitive inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
T
T
Nakagawa
S
S
Komune
T
T
Uemura
N
N
Akaike
D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D003051:Cochlea / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005724:Ganglia / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009475:Neurons, Afferent / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D016318:Quisqualic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013045:Species Specificity
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018377:Neurotransmitter Agents; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D007608:Kainic Acid