Improved gating of a chimeric α7-5HT3A receptor upon mutations at the M2–M3 extracellular loop

Acetylcholine-evoked currents of the receptor chimera α7-5HT3A V201 expressed in Xenopus oocytes are strikingly small when compared to the amount of α-bungarotoxin binding sites detected at the oocyte membrane. Since the chimeric receptor is made of the extracellular N-terminal region of the rat α7 nicotinic acetylcholine receptor and the C-terminal region of the mouse 5-HT3A receptor, which includes the ion channel, we hypothesized that communication between these two regions was not optimal. Here, we show that mutating to aspartate several adjacent positions in the M2–M3 extracellular linker increases current amplitudes to different extents, thus confirming the important role of this region on receptor gating.