Protein kinase C regulation of glycine and gamma-aminobutyric acid release in brain stem auditory nuclei.
Protein kinase C (PKC) can regulate transmitter release in several brain areas. We determined if PKC could regulate the electrically evoked release of radiolabeled glycine (Gly) and gamma-aminobutyric acid (GABA) in dissected samples of several brain stem auditory nuclei, such as the major subdivisions of the cochlear nucleus (CN) and the main nuclei of the superior olivary complex (SOC). The PKC activators, phorbol 12,13-diacetate (PDA) or phorbol 12,13-dibutyrate (PDBu) (3 microM), elevated the release by 1.4- to 2.0-fold. The PKC inhibitor, Ro31-8220 (50 nM), did not alter the release in most of the tissues but blocked the stimulatory effects of PDA and PDBu. This suggested that PKC positively regulates glycinergic and GABAergic release in the sampled nuclei. In the dorsal CN (DCN), Ro31-8220 elevated the release of [(14)C]Gly by 23%, suggesting that PKC negatively regulates glycinergic release in a proportion of DCN synapses. We also determined if PKC could regulate release after unilateral cochlear ablation (UCA). In the anteroventral (AVCN) and posteroventral (PVCN) CN and in the lateral (LSO) and medial (MSO) superior olive, the stimulatory effects of PDBu declined after this lesion and Ro31-8220 failed to alter release. Since UCA failed to alter release in these tissues, the stability of the release correlated with the lack of regulatory capacity of PKC. In the DCN and the medial nucleus of the trapezoid body (MNTB), the stimulatory effects of PDBu persisted after UCA. We previously demonstrated a postablation decline of Gly release in the DCN and elevated GABA release in the MNTB. Treatment of these tissues with Ro31-8220 reversed these changes in release. These findings suggested that PKC regulation persisted in the DCN and MNTB after UCA. Moreover, endogenous regulatory mechanisms activated after UCA probably act through PKC to alter release in these tissues. Thus, limiting PKC activation or activity might ameliorate pathological symptoms that accompany hearing loss and that stem from these plasticities in the DCN and MNTB.
Zhang
J
J
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
Suneja
S K
SK
Potashner
S J
SJ
D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003051:Cochlea / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002250:Carbon Radioisotopes; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D005680:gamma-Aminobutyric Acid; D011493:Protein Kinase C; D005998:Glycine; D004121:Dimethyl Sulfoxide