Protein kinase A and calcium/calmodulin-dependent protein kinase II regulate glycine and GABA release in auditory brain stem nuclei.

We reported previously that unilateral cochlear ablation (UCA) in young adult guinea pigs induced protein kinase C (PKC)-dependent plastic changes in the electrically evoked release of exogenous [14C]glycine ([14C]Gly) or [14C]-gamma-aminobutyric acid ([14C]GABA) in several brain stem auditory nuclei. The present study assessed whether such changes depended on protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII). In the major subdivisions of the cochlear nucleus (CN) and the main nuclei of the superior olivary complex (SOC) dissected from intact animals, dibutyryl-cyclic adenosine monophosphate (DBcAMP) (0.2 mM), a PKA activator, elevated release by 1.6-2.3-fold. The PKA inhibitor, H-89 (2 microM), did not alter the release but blocked the stimulatory effects of DBcAMP. These findings suggested that PKA could positively regulate glycinergic and GABAergic release. After UCA, PKA regulation declined and failed in the ventral CN but persisted in the SOC nuclei. After 145 postablation days, H-89 reversed elevations of [14C]GABA release in the medial nucleus of the trapezoid body (MNTB). A CaMKII inhibitor, KN-93, reversed depressions of [14C]Gly release in the DCN. Thus, the postablation plasticities in these nuclei probably depended on PKA or CaMKII. Both H-89 and KN-93 depressed [14C]Gly release in the lateral superior olive (LSO) and ipsilateral medial superior olive (MSO), suggesting that either kinase was used by endogenous mechanisms in these nuclei to upregulate glycinergic release. In contrast, KN-93 elevated [14C]GABA release in the contralateral MNTB, suggesting a downregulatory action of CaMKII, an action opposite to that of PKA.