Mediation by calcium/calmodulin-dependent protein kinase II of suppression of GABA(A) receptors by NMDA

Science in China. Series C, Life Sciences
D WangTian-Le Xu

Abstract

Using nystatin-perforated whole-cell recording configuration, the modulatory effect of N-methyl-D-aspartate (NMDA) on gamma-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 (I(gaba) and I(Mus)), respectively in the Mg(2+)-free external solution containing 1 mumol/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 gammamol/L), inhibited the NMDA-evoked currents and blocked the NMDA-induced suppression of I(gaba); (ii) when the neurons were incubated in a Ca(2+)-free bath or pre-loaded with a membrane-permeable Ca(2+) chelator, BAPTA AM (10 mumol/L), the inhibitory effect of NMDA on I(GAba) disappeared. Cd(2+) (10 mumol/L) or La(3+) (30 mumol/L), the non-selective blockers of voltage-dependent calcium channels, did not affect the suppression of I(gaba) by NMDA application; (iii) the suppression of I(GAba) by NMDA was inhibited by KN-62, a calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results indicated that th...Continue Reading

References

Nov 1, 1994·The Journal of Membrane Biology·M MartinaE Cherubini
Jun 1, 1997·Comparative Biochemistry and Physiology. Part A, Physiology·T L XuN Akaike
Feb 28, 1998·Pflügers Archiv : European journal of physiology·L G AguayoL S Satin
Aug 5, 1998·British Journal of Pharmacology·T L XuN Akaike

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