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1. Na channel reversal potentials were studied in perfused voltage clamped squid giant axons. The concentration dependence of ion selectivity was determined with both external and internal changes in Na and ammonium concentrations. 2. A tenfold change in the internal ammonium activity results in a 42 mV shift in the reversal potential, rather than the 56 mV shift expected from the Goldman, Hodgkin, Katz equation for a constant PNa/PNH4 ratio. However, changing [Na]o tenfold at constant internal [NH4] gives approximately the expected 56 mV shift. Therefore, the apparent channel selectivity depends upon the internal ammonium concentration but not the external Na concentration. 3. With ammonium outside and Na inside, the calculated permeability ratio is nearly constant, regardless of the permeant ion concentration. 4. Internal Cs ions can alter the Na/K permeability ratio. 5. The results are considered in terms of a three-barrier, two-site ionic permeation model.

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