Hydrogen ions block sodium channels in nerve cells, reducing sodium permeability. This block is voltage-dependent, with higher reductions at more positive voltages. The model suggests that hydrogen ions enter the open sodium channel and bind there, preventing sodium ion passage. The voltage dependence arises because the binding site is located across the membrane, allowing bound ions to respond to the membrane potential. The dissociation constant of hydrogen ions from the channel site is 3.9 × 10⁻⁶ M (pKa 5.4), similar to a carboxylic acid. The acid site is about one-quarter of the way across the membrane from the outside. Hydrogen ions also shift the responses of sodium channel "gates" to voltage, likely by altering the surface potential of the nerve. Calcium ions also block sodium channels, though the effects are less voltage-dependent. Hydrogen ions reduce sodium currents responsible for nerve action potentials. The effects of hydrogen ions on sodium permeability are similar to the titration of an acid. The new finding is that a given concentration of hydrogen ions blocks sodium currents more or less depending on the potential across the nerve membrane. A simple theory suggests that hydrogen ions enter the sodium channel and bind there, preventing sodium ion passage. Being inside the membrane, the hydrogen ion would respond to membrane voltage. A kinetic model for ionic blockage of channels is developed. The applicability of this model to the data for hydrogen ion blockage of sodium channels and the values of the model’s parameters provide new information about the inside of the sodium channel. The information accords well with the idea that there is an acidic group inside the sodium channel. The study used voltage-clamped frog nerve fibers to measure the effects of hydrogen ions on sodium currents. The nodes of Ranvier were voltage clamped, and the effects of varying pH on sodium currents were measured. The results showed that hydrogen ions reduce sodium currents at all voltages, with the most significant reduction at lower pH. The voltage dependence of the block is explained by the position of the binding site within the membrane. The study also found that hydrogen ions shift the responses of sodium channel gates to voltage, likely by altering the surface potential of the nerve. The results suggest that the sodium channel has voltage-sensitive gates that open to reveal a rigid pore, through which sodium ions must pass. The blocking site is likely a carboxylic acid group in the selectivity filter, located about one-quarter of the way across the membrane from the outside. The voltage dependence of both hydrogen and calcium blocking places this acid group and the filter about one-quarter of the way into the membrane from the outside. When hydrogen blockage is corrected for, the changes in gating caused by hydrogen can be seen as simple shifts in the responses of the sodium channel gates to voltage. It is likely that protons cause these shifts by changing the surface potential of the axon membrane.Hydrogen ions block sodium channels in nerve cells, reducing sodium permeability. This block is voltage-dependent, with higher reductions at more positive voltages. The model suggests that hydrogen ions enter the open sodium channel and bind there, preventing sodium ion passage. The voltage dependence arises because the binding site is located across the membrane, allowing bound ions to respond to the membrane potential. The dissociation constant of hydrogen ions from the channel site is 3.9 × 10⁻⁶ M (pKa 5.4), similar to a carboxylic acid. The acid site is about one-quarter of the way across the membrane from the outside. Hydrogen ions also shift the responses of sodium channel "gates" to voltage, likely by altering the surface potential of the nerve. Calcium ions also block sodium channels, though the effects are less voltage-dependent. Hydrogen ions reduce sodium currents responsible for nerve action potentials. The effects of hydrogen ions on sodium permeability are similar to the titration of an acid. The new finding is that a given concentration of hydrogen ions blocks sodium currents more or less depending on the potential across the nerve membrane. A simple theory suggests that hydrogen ions enter the sodium channel and bind there, preventing sodium ion passage. Being inside the membrane, the hydrogen ion would respond to membrane voltage. A kinetic model for ionic blockage of channels is developed. The applicability of this model to the data for hydrogen ion blockage of sodium channels and the values of the model’s parameters provide new information about the inside of the sodium channel. The information accords well with the idea that there is an acidic group inside the sodium channel. The study used voltage-clamped frog nerve fibers to measure the effects of hydrogen ions on sodium currents. The nodes of Ranvier were voltage clamped, and the effects of varying pH on sodium currents were measured. The results showed that hydrogen ions reduce sodium currents at all voltages, with the most significant reduction at lower pH. The voltage dependence of the block is explained by the position of the binding site within the membrane. The study also found that hydrogen ions shift the responses of sodium channel gates to voltage, likely by altering the surface potential of the nerve. The results suggest that the sodium channel has voltage-sensitive gates that open to reveal a rigid pore, through which sodium ions must pass. The blocking site is likely a carboxylic acid group in the selectivity filter, located about one-quarter of the way across the membrane from the outside. The voltage dependence of both hydrogen and calcium blocking places this acid group and the filter about one-quarter of the way into the membrane from the outside. When hydrogen blockage is corrected for, the changes in gating caused by hydrogen can be seen as simple shifts in the responses of the sodium channel gates to voltage. It is likely that protons cause these shifts by changing the surface potential of the axon membrane.