CA2-PERMEABILITY OF MUSCLE NICOTINIC ACETYLCHOLINE-RECEPTOR IS INCREASED BY EXPRESSION OF THE EPSILON-SUBUNIT()

We have expressed muscle embryonic (alpha beta gamma delta) and adult (a:alpha beta delta epsilon) nicotinic acetylcholine receptors in Xeno pus Laevis oocytes and measured their current reversal potentials in t he presence of extracellular Na+, Ca2+, Sr2+ Or Ba2+ ions. The ionic p ermeability ratio PCa2+/ PNa+ was increased about 3 fold by the change in the subunit composition of the nicotinic acetylcholine receptor (r eplacement of the gamma by the epsilon subunit). A similar increase wa s also found when permeability to Ba2+ and Sr2+ ions was studied. Comp arison of the nicotinic Ca2+ currents recorded from oocytes injected w ith embryonic or adult receptor subunit combinations also showed that the Ca2+ influx was significantly increased by expressing the epsilon subunit. This increase was estimated to change the contribution of the Ca2+ current to the total net inward current from 0.8% (in the case o f the alpha beta gamma delta receptor) to 2.5% (in the case of the alp ha beta delta epsilon receptor). Taken together, these results suggest that important modifications in the acetylcholine-mediated Ca2+ influ x occurred during muscle innervation and underline the role of the nic otinic receptor in the developmental regulation of Ca2+ influx.