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

Autor:	Jang IS; Kyungpook National University, Daegu, Republic of Korea (I.S.J., M.Na); Kumamoto Health Science University, Kumamoto, Japan (K.N.); Kyushu University, Fukuoka, Japan (M.No); Kitamoto Hospital, Saitama, Japan (N.K., N.A.); Fukuoka University, Fukuoka, Japan (S.K.); and Kumamoto Kinoh Hospital, Kumamoto, Japan (H.N., N.A.)., Nakamura M; Kyungpook National University, Daegu, Republic of Korea (I.S.J., M.Na); Kumamoto Health Science University, Kumamoto, Japan (K.N.); Kyushu University, Fukuoka, Japan (M.No); Kitamoto Hospital, Saitama, Japan (N.K., N.A.); Fukuoka University, Fukuoka, Japan (S.K.); and Kumamoto Kinoh Hospital, Kumamoto, Japan (H.N., N.A.)., Nonaka K; Kyungpook National University, Daegu, Republic of Korea (I.S.J., M.Na); Kumamoto Health Science University, Kumamoto, Japan (K.N.); Kyushu University, Fukuoka, Japan (M.No); Kitamoto Hospital, Saitama, Japan (N.K., N.A.); Fukuoka University, Fukuoka, Japan (S.K.); and Kumamoto Kinoh Hospital, Kumamoto, Japan (H.N., N.A.)., Noda M; Kyungpook National University, Daegu, Republic of Korea (I.S.J., M.Na); Kumamoto Health Science University, Kumamoto, Japan (K.N.); Kyushu University, Fukuoka, Japan (M.No); Kitamoto Hospital, Saitama, Japan (N.K., N.A.); Fukuoka University, Fukuoka, Japan (S.K.); and Kumamoto Kinoh Hospital, Kumamoto, Japan (H.N., N.A.)., Kotani N; Kyungpook National University, Daegu, Republic of Korea (I.S.J., M.Na); Kumamoto Health Science University, Kumamoto, Japan (K.N.); Kyushu University, Fukuoka, Japan (M.No); Kitamoto Hospital, Saitama, Japan (N.K., N.A.); Fukuoka University, Fukuoka, Japan (S.K.); and Kumamoto Kinoh Hospital, Kumamoto, Japan (H.N., N.A.)., Katsurabayashi S; Kyungpook National University, Daegu, Republic of Korea (I.S.J., M.Na); Kumamoto Health Science University, Kumamoto, Japan (K.N.); Kyushu University, Fukuoka, Japan (M.No); Kitamoto Hospital, Saitama, Japan (N.K., N.A.); Fukuoka University, Fukuoka, Japan (S.K.); and Kumamoto Kinoh Hospital, Kumamoto, Japan (H.N., N.A.)., Nagami H; Kyungpook National University, Daegu, Republic of Korea (I.S.J., M.Na); Kumamoto Health Science University, Kumamoto, Japan (K.N.); Kyushu University, Fukuoka, Japan (M.No); Kitamoto Hospital, Saitama, Japan (N.K., N.A.); Fukuoka University, Fukuoka, Japan (S.K.); and Kumamoto Kinoh Hospital, Kumamoto, Japan (H.N., N.A.)., Akaike N; Kyungpook National University, Daegu, Republic of Korea (I.S.J., M.Na); Kumamoto Health Science University, Kumamoto, Japan (K.N.); Kyushu University, Fukuoka, Japan (M.No); Kitamoto Hospital, Saitama, Japan (N.K., N.A.); Fukuoka University, Fukuoka, Japan (S.K.); and Kumamoto Kinoh Hospital, Kumamoto, Japan (H.N., N.A.) akaike.sachin715@juryo.or.jp.
Jazyk:	angličtina
Zdroj:	The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2023 Sep; Vol. 386 (3), pp. 331-343. Date of Electronic Publication: 2023 Jun 30.
DOI:	10.1124/jpet.123.001599
Abstrakt:	The effects of a general anesthetic xenon (Xe) on spontaneous, miniature, electrically evoked synaptic transmissions were examined 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 sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xe presynaptically inhibited spontaneous glycinergic transmission, the effect of which was resistant to tetrodotoxin, Cd 2+ , extracellular Ca 2+ , thapsigargin (a selective sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase inhibitor), SQ22536 (an adenylate cyclase inhibitor), 8-Br-cAMP (membrane-permeable cAMP analog), ZD7288 (an hyperpolarization-activated cyclic nucleotide-gated channel blocker), chelerythrine (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, spontaneous and evoked glutamatergic transmissions were also inhibited by Xe in a KT5720-sensitive manner. Our results suggest that Xe decreases glycinergic and glutamatergic spontaneous and evoked transmissions at the presynaptic level in a PKA-dependent manner. These presynaptic responses are independent of Ca 2+ dynamics. We conclude that PKA can be the main molecular target of Xe in the inhibitory effects on both inhibitory and excitatory neurotransmitter release. SIGNIFICANCE STATEMENT: Spontaneous and evoked glycinergic and glutamatergic transmissions were investigated using the whole-cell patch clamp technique in rat spinal sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xenon (Xe) significantly inhibited glycinergic and glutamatergic transmission presynaptically. As a signaling mechanism, protein kinase A was responsible for the inhibitory effects of Xe on both glycine and glutamate release. These results may help understand how Xe modulates neurotransmitter release and exerts its excellent anesthetic properties. (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze:	MEDLINE
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