Protein kinase A and C signaling induces bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus neurons

Abstract Previous studies have suggested that bilirubin can potentiate GABA/glycinergic synaptic transmission in lateral superior olivary nucleus neurons, but the cellular mechanism has not been defined. The present study evaluated the possible roles of protein kinase A (PKA) and C (PKC) in bilirubi...

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Published in:Brain research 2010-08, Vol.1348, p.30-41
Main Authors: Li, Chun-Yan, Shi, Hai-Bo, Chen, Zheng-Nong, Ye, Hai-Bo, Song, Ning-ying, Yin, Shan-Kai
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Antioxidants - pharmacology
Benzophenanthridines - pharmacology
Bilirubin
Bilirubin - pharmacology
Cochlear Nucleus - cytology
Colforsin - pharmacology
Cyclic AMP-Dependent Protein Kinases - metabolism
Enzyme Activation - drug effects
GABAergic
gamma-Aminobutyric Acid - metabolism
Glycine - metabolism
Glycinergic
In Vitro Techniques
Isoquinolines - pharmacology
Neural Inhibition - drug effects
Neurology
Neurons - drug effects
Patch-Clamp Techniques - methods
Phorbol Esters - pharmacology
Protein kinase A
Protein kinase C
Protein Kinase C - metabolism
Rats
Signal Transduction - drug effects
Sulfonamides - pharmacology
Synaptic Transmission - drug effects
Ventral cochlear nucleus
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Summary:Abstract Previous studies have suggested that bilirubin can potentiate GABA/glycinergic synaptic transmission in lateral superior olivary nucleus neurons, but the cellular mechanism has not been defined. The present study evaluated the possible roles of protein kinase A (PKA) and C (PKC) in bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus (VCN) neurons. VCN neurons were acutely isolated from postnatal 10-12-day-old (P10-12) rats and were voltage-clamped in whole-cell mode. Miniature inhibitory postsynaptic currents (mIPSC) frequencies, but not amplitude, were increased by bilirubin. Forskolin (PKA activator) and H-89 (PKA inhibitor) also individually increased mIPSCs frequency, with an additional increase induced by co-incubation with bilirubin and H-89. Pretreatment with forskolin blocked bilirubin potentiation. mIPSC frequency was not altered by phorbol 12,13-diacetate (PKC activator), but mIPSC frequency was increased following co-application of bilirubin. The mIPSC frequency was increased by chelerythrine (PKC inhibitor), and then further increased after the addition of bilirubin. Neither H-89, forskolin, nor PDA, nor their co-application with bilirubin affected mIPSC amplitudes of GABA-activated (IGABA )/glycine-activated (Igly ) currents, suggesting a presynaptic locus of activity. Chelerythrine decreased the mIPSC amplitudes and IGABA /Igly , suggesting a postsynaptic locus of activity. These data suggest that both PKA and PKC can modulate GABA and glycine release in rat VCN neurons. Bilirubin facilitates transmitter release via presynaptic PKA activation, which might provide insight into the cellular mechanism underlying bilirubin-induced hearing dysfunction.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2010.06.022