British journal of pharmacology
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The present studies were designed to test the hypothesis that neuronal-specific protein kinase Cgamma (PKCgamma) plays a critical role in acute ethanol withdrawal hyper-responsiveness in spinal cord. Patch-clamp studies were carried out in motor neurons in neonatal rat spinal cord slices. Postsynaptic currents were evoked by brief pulses of 2 mM N-methyl-D-aspartic acid (NMDA) in the presence of bicuculline methiodide 10 microM; strychnine 5 microM and tetrodotoxin 0.5 microM. ⋯ Exposure to ethanol (100 mM) induced PKCgamma translocation from the nucleus to cytoplasm in motor neurons. Pretreatment with the gamma-isozyme-specific peptide PKC inhibitor, gammaV5-3, blocked ethanol-induced translocation and also blocked withdrawal hyper-responsiveness. The results show that PKCgamma mediates ethanol withdrawal hyper-responsiveness in spinal motor neurons; the results may be relevant to some symptoms of ethanol withdrawal in vivo.