ELEVATION OF BASAL PROTEIN-KINASE-C ACTIVITY INCREASES ETHANOL SENSITIVITY OF GABA(A) RECEPTORS IN RAT HIPPOCAMPAL CA1 PYRAMIDAL NEURONS

The ability of ethanol to enhance GABAA receptor function remains cont roversial; conflicting observations have been made even in the same br ain region, and when using apparently similar methodologies. In this s tudy we characterized a single protocol variable, the initial incubati on temperature of brain slices, that had dramatic effects on the ethan ol sensitivity of GABA(A) inhibitory postsynaptic currents (IPSCs) rec orded from rat hippocampal CA1 pyramidal neurons, Incubation of hippoc ampal slices at relatively low temperatures (11-15 degrees C) immediat ely after slice preparation significantly affected a number of physiol ogical and biochemical parameters, Such slices showed a decrease in ex tracellular inhibitory postsynaptic potential amplitude, a significant increase in the ethanol sensitivity of GABA(A) IPSCs in CA1 pyramidal neurons, no change in pentobarbital or flunitrazepam potentiation of IPSCs, and an increase in basal protein kinase C (PKC) activity relati ve to slices incubated at 31-33 degrees C, In addition, the increase i n ethanol sensitivity of GABA(A) IPSCs was blocked by chelerythrine, a selective inhibitor of PKC. These results suggest that differences in hippocampal slice incubation protocols may have contributed to the di sparate results of previous investigations of ethanol modulation of GA BA(A) receptor-mediated synaptic transmission in the rat hippocampus. In addition, these findings provide further evidence that PKC activity positively modulates the interaction between ethanol and GABA(A) rece ptors in the mammalian brain.