Fractional Ca2+ current through human neuronal alpha7 nicotinic acetylcholine receptors

The neuronal 7 nicotinic acetylcholine (ACh) receptor is believed to be a highly Ca2+ permeable ligand-gated receptor-channel. However, the contribution of Ca2+ to cationic current generated by ACh has not yet been directly measured to date. Simultaneous fluorescence and whole-cell current measurements using the Ca2+ indicator dye fura-2 were made inGH4C1pituitary cells stably expressing human 7 receptors and the fractional Ca2+ current (the proportion of whole-cell current carried by Ca2+; Pf ) was determined. We report that the Pf value was 11.4±1.3%. This value was significantly larger than Pf of human L248T7 receptor mutant (Pf = 6.3±1.0%) and of rat 7 receptor (Pf = 8.8±1.5%) both determined in transiently transfected GH4C1 cells. In our knowledge, the findings here reported indicate the human 7 receptors are the most Ca2+ conductive homomeric ligand-gated receptor-channels expressed in a heterologous cell system.