Enhancement of GABA-mediated inhibition of rat medial vestibular nucleus neurons by the neurosteroid 20-hydroxyecdysone.
In vivo electrophysiological and patch-clamp studies were performed to determine whether 20-hydroxyecdysone (20-HE), a neurosteroid, influenced neuronal activities of the medial vestibular nucleus (MVN) using chloral hydrate-anesthetized rats and dissociated MVN neurons, respectively. Single neuronal activities of MVN were extracellularly recorded with a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. Each micropipette was filled with 20-HE, glutamate, bicuculline or 2 M NaCl. These chemicals were applied microiontophoretically to the immediate vicinity of the target neurons. Microiontophoretically applied 20-HE (20-80 nA) dose-dependently decreased rotation-induced firings of both type I and II neurons, which were identified according to their responses to horizontal sinusoidal rotations. Microiontophoretically applied bicuculline, a GABAA receptor antagonist, inhibited 20-HE-induced decreases in neuronal firing of MVN. These findings suggest that 20-HE potentiates the action of GABA, probably by acting directly on the GABAA receptor of MVN neurons. In addition, microiontophoretically applied 20-HE decreased firings induced by glutamate in both type I and II neurons. This decrease by 20-HE was also antagonized with bicuculline. Furthermore, the effects of 20-HE on GABA-induced currents in acutely dissociated MVN neurons were investigated using the whole-cell patch-clamp technique. Under voltage-clamp conditions, GABA (10 microM)-induced currents were potentiated in the presence of 20-HE (100 microM). These findings suggest that 20-HE inhibits MVN neurons by acting on the modulatory site on GABA receptor-ion channel complexes to potentiate GABA inhibition.
Okada
M
M
Department of Otorhinolaryngology, Hiroshima University School of Medicine, Japan.
Ishihara
K
K
Sasa
M
M
Izumi
R
R
Yajin
K
K
Harada
Y
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004441:Ecdysterone / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012399:Rotation; D009435:Synaptic Transmission / Q000187:drug effects; D014724:Vestibular Function Tests; D014726:Vestibular Nuclei / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D004441:Ecdysterone; D005680:gamma-Aminobutyric Acid