Next we tested whether the CNIH-2-mediated increase in GluA surface protein observed in heterologous expression systems is also true for native AMPARs in neurons. CNIH-2 was over-expressed in CA1 pyramidal neurons of organotypic hippocampal slice cultures and functional AMPAR surface expression was evaluated by quantifying glutamate-evoked currents in somatic outside-out patches in the presence of the desensitization blocker trichlormethiazide. Compared to sham-infected control neurons (0.96±0.12 nA; n = 14), CNIH-2 over-expression doubled current amplitudes (2.12±0.25 nA; n = 11; p<0.0001) (Fig. 1C). These results demonstrate that CNIH-2 promotes functional surface expression of AMPARs in both heterologous cells and primary neurons most likely due to a gain in the amount of surface protein. In addition, AMPAR currents could increase by CNIH-2-mediated modulation of their biophysical properties, i. e. an increase in single channel conductance [28].
