Figure 1.
The positive allosteric modulators aniracetam and CX614 slow deactivation more profoundly than cyclothiazide at GluR2 (flop) receptors. A, Electrophysiological responses of GluR2 (flop) expressed on outside-out patches of transiently transfected HEK 293 cells. Top traces show the kinetics of deactivation, the decay of the peak response after a brief (1 ms) pulse of 3 mm quisqualate. Bottom traces show the kinetics of desensitization, the decay during a prolonged (500 ms) pulse of quisqualate. Responses are shown for patches with no drug or with 5 mm aniracetam, 100 μm CX614, or 100 μm cyclothiazide. Single-exponential fits are superimposed on the trace. Open-tip potentials are shown above the control traces. Note that desensitization by CTZ of GluR2o is only partially modulated compared with the flip isoform in which desensitization is virtually blocked. B, Chemical structures of aniracetam and CX614. The atoms of aniracetam and CX614 are numbered using smaller font, with oxygen atoms in red and carbon atoms in black, and the rings are numbered using a larger font.