Protein Kinase A Is Responsible for the Presynaptic Inhibition of Glycinergic and Glutamatergic Transmissions by Xenon in Rat Spinal Cord and Hippocampal CA3 Neurons

초록

The effects of a general anesthetic xenon (Xe) on spontaneous, miniature, electrically evoked synaptic transmissions were ex-amined using the "synapse bouton preparation," with which we can clearly evaluate pure synaptic responses and accurately quantify pre-and postsynaptic transmissions. Glycinergic and glutamatergic transmissions were investigated in rat spinal sa-cral dorsal commissural nucleus and hippocampal CA3 neu-rons, respectively. Xe presynaptically inhibited spontaneous glycinergic transmission, the effect of which was resistant to te-trodotoxin, Cd2+, extracellular Ca2+, thapsigargin (a selective sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor), SQ22536 (an adenylate cyclase inhibitor), 8-Br-cAMP (mem-brane-permeable cAMP analog), ZD7288 (an hyperpolarization-activated cyclic nucleotide-gated channel blocker), chelerythr-ine (a PKC inhibitor), and KN-93 (a CaMKII inhibitor) while being sensitive to PKA inhibitors (H-89, KT5720, and Rp-cAMPS). Moreover, Xe inhibited evoked glycinergic transmission, which was canceled by KT5720. Like glycinergic transmission, spon-taneous and evoked glutamatergic transmissions were also inhibited by Xe in a KT5720-sensitive manner. Our results sug-gest that Xe decreases glycinergic and glutamatergic sponta-neous and evoked transmissions at the presynaptic level in a PKA-dependent manner. These presynaptic responses are in-dependent of Ca2+ dynamics. We conclude that PKA can be the main molecular target of Xe in the inhibitory effects on both inhibitory and excitatory neurotransmitter release.

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