Structure, pharmacology and function of GABA-A receptors in cochlear outer hair cells.
There is evidence that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is released from some efferent olivocochlear nerve endings terminating at outer hair cells (OHCs). Using monoclonal antibodies against postsynaptic GABAA receptor from bovine cerebral cortex we confirm the presence of GABA and benzodiazepine bindings sites of alpha- and beta-subunits of GABAA receptors at the basal pole of isolated OHCs. Whole-cell recording with viable OHCs revealed that the application of 10(-3)-10(-8) M GABA to the cell surface was followed by a concentration-dependent hyperpolarization of the outer cell membrane. Hyperpolarization was increased in the presence of 2.5 x 10(-5) M chlorazepate, a benzodiazepine derivative. Electrophysiological effects caused by GABA alone or in combination with chlorazepate were specifically inhibited by 10(-6) M of the GABA-receptor antagonist picrotoxin. Moreover, 10(-5)-10(-7) M GABA caused reversible slow elongation of the cylindrical hair cell body in OHCs examined. These neurotransmitter-induced motile responses were specifically blocked by 10(-4) M picrotoxin. The results suggest that a subpopulation of OHCs express alpha- and beta-subunits of GABAA receptors which both form a GABA/benzodiazepine-receptor complex at the basal pole of isolated OHCs. These receptors are thought to allow GABA which is released from efferent auditory nerve terminals to bind to the cell surface of OHCs, resulting in GABAA-receptor activation. This probably gates a GABAA-receptor-associated chloride channel in the postsynaptic OHC membrane, allowing hyperpolarization and elongation of the cell.
Plinkert
P K
PK
Department of Otorhinolaryngology, University of Tübingen, Germany.
Gitter
A H
AH
Möhler
H
H
Zenner
H P
HP
D000818:Animals; D003009:Clorazepate Dipotassium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D003009:Clorazepate Dipotassium; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid