Ca(2+)-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 (alpha beta delta epsilon) nicotinic acetylcholine receptors in Xenopus Laevis oocytes and measured their current reversal potentials in the presence of extracellular Na+, Ca2+, Sr2+ or Ba2+ ions. The ionic permeability ratio PCa2+/PNa+ was increased about 3 fold by the change in the subunit composition of the nicotinic acetylcholine receptor (replacement of the gamma by the epsilon subunit). A similar increase was also found when permeability to Ba2+ and Sr2+ ions was studies. Comparison of the nicotinic Ca2+ currents recorded from oocytes injected with 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 of the alpha beta gamma delta receptor) to 2.5% (in the case of the alpha beta delta epsilon receptor). Taken together, these results suggest that important modifications in the acetylcholine-mediated Ca2+ influx occurred during muscle innervation and underline the role of the nicotinic receptor in the developmental regulation of Ca2+ influx.