Cross-talk between NMDA and GABA(A) receptors in cultured neurons of the rat inferior colliculus.

Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels, a process called cross-talk. The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system, respectively. Currently, cross-talk between the NMDA receptor and the GABAA receptor, particularly in the central auditory system, is not well understood. In the present study, we investigated functional interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus, which is an important nucleus in the central auditory system. We found that the currents induced by aspartate at 100 μmol L−1 were suppressed by the pre-perfusion of GABA at 100 μmol L−1, indicating cross-inhibition of NMDA receptors by activation of GABAA receptors. Moreover, we found that the currents induced by GABA at 100 μmol L−1 (IGABA) were not suppressed by the pre-perfusion of 100 μmol L−1 aspartate, but those induced by GABA at 3 μmol L−1 were suppressed, indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors. In addition, inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+, however, CdCl2 effectively attenuated the inhibition of IGABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L−1 BAPTA, a membrane-permeable Ca2+ chelator, suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors, rather than voltage-dependent Ca2+ channels. Finally, KN-62, a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII), reduced the inhibition of IGABA by aspartate, indicating the involvement of CaMKII in this cross-inhibition. Our study demonstrates a functional interaction between NMDA and GABAA receptors in the inferior colliculus of rats. The presence of cross-talk between these receptors suggests that the mechanisms underlying information processing in the central auditory system may be more complex than previously believed.