Abstract
Using nystatin-perforated whole-cell recording configuration, the modulatory effect of N-methyl-D-aspartate (NMDA) on γ-aminobutyric acid (GABA)-activated whole-cell currents was investigated in neurons freshly dissociated from the rat sacral dorsal commissural nucleus (SDCN). The results showed that: (i) NMDA suppressed GABA-and muscimol (Mus)-activated currents (Igaba and IMus), respectively in the Mg2+-free external solution containing 1 μmol/L glycine at a holding potential (V H ) of −40 mV in SDCN neurons. The selective NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 100 γmol/L), inhibited the NMDA-evoked currents and blocked the NMDA-induced suppression of Igaba; (ii) when the neurons were incubated in a Ca2+-free bath or pre-loaded with a membrane-permeable Ca2+ chelator, BAPTA AM (10 μmol/L), the inhibitory effect of NMDA on IGAba disappeared. Cd2+ (10 μmol/L) or La3+ (30 μmol/L), the non-selective blockers of voltage-dependent calcium channels, did not affect the suppression of Igaba by NMDA application; (iii) the suppression of IGAba by NMDA was inhibited by KN-62, a calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results indicated that the inhibition of GABA response by NMDA is Ca2+-dependent and CaMKII is involved in the process of the Ca2+-dependent inhibition.
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Wang, D., Lü, H. & Xu, T. Mediation by calcium/calmodulin-dependent protein kinase II of suppression of GABAA receptors by NMDA. Sci. China Ser. C.-Life Sci. 43, 655–662 (2000). https://doi.org/10.1007/BF02882287
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DOI: https://doi.org/10.1007/BF02882287