Bilirubin potentiates inhibitory synaptic transmission in lateral superior olive neurons of the rat.
Bilirubin is a well-known neurotoxin that can result in multiple neurologic deficits. Previous studies have suggested that bilirubin affects aspects of synaptic transmission; however the acute effects of bilirubin on synaptic transmission have not been examined in real-time. In this study, using whole-cell voltage-clamp recordings, we observed the effect of bilirubin on inhibitory postsynaptic currents (IPSC) in postnatal 13-15-day-old neurons dissociated from lateral superior olive nuclei (LSO), one of the brainstem auditory nucleus that are highly vulnerable to bilirubin. The results showed that 10(-5)M bilirubin increased the frequency of spontaneous IPSC without causing change in their amplitudes or in the response to bath applied glycine, suggesting a presynaptic locus for the action. In the presence of tetrodotoxin, the frequency of miniature IPSC was also potentiated by 10(-5)M bilirubin. The facilitation by bilirubin was concentration dependent and increased with an increase in exposure time. Bicuculline only partially reduced the action of bilirubin. The action of bilirubin was observed in extracellular Ca(2+)-free ([Ca(2+)](o) free) solution but was fully occluded by pretreatment with BAPTA-AM in [Ca(2+)](o) free solution. Thus, in LSO neurons, bilirubin facilitates inhibitory synaptic transmission, in a manner independent of voltage-activated Na(+) and Ca(2+) channels but dependent on presynaptic [Ca(2+)](i). The increase of inhibitory synaptic transmission in response to acute bilirubin is a novel effect of bilirubin on the central nervous system and may have implications for neurotoxicity and the impairment of auditory transduction seen in hyperbilirubinemia.
Shi
Hai-Bo
HB
Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Kakazu
Yasuhiro
Y
Shibata
Shumei
S
Matsumoto
Nozomu
N
Nakagawa
Takashi
T
Komune
Shizuo
S
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001663:Bilirubin / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009847:Olivary Nucleus / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D002614:Chelating Agents; D018756:GABA Antagonists; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D013779:Tetrodotoxin; D004533:Egtazic Acid; D013331:Strychnine; D001663:Bilirubin; D001640:Bicuculline