title: Protein kinases regulate glycine receptor binding in brain stem auditory nuclei after unilateral cochlear ablation.
abstract: Glycinergic synaptic inhibition is part of acoustic information processing in brain stem auditory pathways and contributes to the regulation of neuronal excitation. We found previously that unilateral cochlear ablation (UCA) in young adult guinea pigs decreased [3H]strychnine binding activity in several brain stem auditory nuclei. This study determined if the UCA-induced deficit could be regulated by protein kinase C (PKC), protein kinase A (PKA) or Ca2+/calmodulin-dependent protein kinase II (CaMKII). The specific binding of [3H]strychnine was measured in slices of the dorsal (DCN), posteroventral (PVCN) and anteroventral (AVCN) cochlear nucleus (CN), the lateral (LSO) and medial (MSO) superior olive, and the inferior colliculus (IC) 145 days after UCA. Tissues from age-matched unlesioned animals served as controls. UCA induced deficits in specific binding in the AVCN, PVCN, and LSO on the ablated side and in the MSO bilaterally. These deficits were reversed by 3 microM phorbol 1,2-dibutyrate, a PKC activator, or 0.2 mM dibutyryl-cAMP, a PKA activator. However, 50 nM Ro31-8220, a PKC inhibitor, and 2 microM H-89, a PKA inhibitor, had no effect in unlesioned controls and after UCA. In contrast, 4 microM KN-93, a CaMKII inhibitor, relieved or reversed the UCA-induced binding deficits and elevated binding in the IC. These findings suggest that a UCA-induced down-regulation of glycine receptor synthesis may have occurred via reduced phosphorylation of proteins that control receptor synthesis; this effect was reversed by diminishing CaMKII activity or increasing PKC and PKA activity.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030-3401, USA.
authors.forename: Leqin
authors.initials: L
authors.lastname: Yan
authors.forename: Sanoj K
authors.initials: SK
authors.lastname: Suneja
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Potashner
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000502:physiology*; D001933:Brain Stem / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D003051:Cochlea / Q000293:injuries* / Q000503:physiopathology; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality; D006168:Guinea Pigs; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000494:pharmacology / Q000502:physiology*; D018009:Receptors, Glycine / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D018009:Receptors, Glycine; D014316:Tritium; D011494:Protein Kinases