The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat.
Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease.
Department of Otorhinolaryngology-Head &Neck Surgery Affiliated Sixth People's Hospital of Shanghai Jiaotong University, Shanghai, P.R. China.
Xiao-Juan
XJ
Chen
Department of Otorhinolaryngology-Head &Neck Surgery Affiliated Sixth People's Hospital of Shanghai Jiaotong University, Shanghai, P.R. China.
Hui-Qun
HQ
Zhou
Department of Otorhinolaryngology-Head &Neck Surgery Affiliated Sixth People's Hospital of Shanghai Jiaotong University, Shanghai, P.R. China.
Hai-Bo
HB
Ye
Department of Otorhinolaryngology-Head &Neck Surgery Affiliated Sixth People's Hospital of Shanghai Jiaotong University, Shanghai, P.R. China.
Chun-Yan
CY
Li
Department of Otorhinolaryngology-Head &Neck Surgery Affiliated Sixth People's Hospital of Shanghai Jiaotong University, Shanghai, P.R. China.
Wei-Tian
WT
Zhang
D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D008107:Liver Diseases / Q000150:complications; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D000857:Olfaction Disorders / Q000139:chemically induced / Q000209:etiology; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001663:Bilirubin