Document Detail


Protein kinase A and C signaling induces bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus neurons.
MedLine Citation:
PMID:  20561511     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (I(GABA))/glycine-activated (I(gly)) currents, suggesting a presynaptic locus of activity. Chelerythrine decreased the mIPSC amplitudes and I(GABA)/I(gly), 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.
Authors:
Chun-Yan Li; Hai-Bo Shi; Zheng-Nong Chen; Hai-Bo Ye; Ning-Ying Song; Shan-Kai Yin
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-16
Journal Detail:
Title:  Brain research     Volume:  1348     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-29     Completed Date:  2010-11-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  30-41     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Antioxidants / pharmacology
Benzophenanthridines / pharmacology
Bilirubin / pharmacology*
Cochlear Nucleus / cytology*
Cyclic AMP-Dependent Protein Kinases / metabolism*
Enzyme Activation / drug effects
Forskolin / pharmacology
Glycine / metabolism
Isoquinolines / pharmacology
Neural Inhibition / drug effects
Neurons / drug effects*
Patch-Clamp Techniques / methods
Phorbol Esters / pharmacology
Protein Kinase C / metabolism*
Rats
Signal Transduction / drug effects*
Sulfonamides / pharmacology
Synaptic Transmission / drug effects*
gamma-Aminobutyric Acid / metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Benzophenanthridines; 0/Isoquinolines; 0/Phorbol Esters; 0/Sulfonamides; 127243-85-0/H 89; 24928-15-2/phorbol-12,13-diacetate; 34316-15-9/chelerythrine; 56-12-2/gamma-Aminobutyric Acid; 56-40-6/Glycine; 635-65-4/Bilirubin; 66428-89-5/Forskolin; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.13/Protein Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Learned and cognitive controls of food intake.
Next Document:  Hepatocyte or serum albumin protein carbonylation by oxidized fructose metabolites: glyceraldehyde o...