Both α and β subunits contribute to the distinct responses of hENaC and mENaC to external Cu2+. The effects of 10 μm Cu2+ on whole cell currents were examined in oocytes expressing αβγ hENaC (A, HαHβHγ), α mENaC with β and γ hENaC (B, MαHβHγ), α and γ hENaC with β mENaC (C, HαMβHγ), α and β hENaC and γ mENaC (D, HαHβMγ), or αβγ mENaC (E, MαMβMγ). Each recording represents five observations. The gray bars show the presence of 10 μm amiloride. F, relative current (ICu/I, n = 5). Bath solution was buffered with 10 mm HEPES. The ICu/I values were the ratios of amiloride-sensitive currents measured after and before 10 μm Cu2+ applications. Rundown was not deducted from the observed current decreases in this and all subsequent figures. The solid bars indicate that the values are significantly different from that of αβγhENaC obtained in the same batches of oocytes (p < 0.05 for MαHβHγ, p < 0.001 for HαMβHγ and MαMβMγ).