This paper investigates the effects of various quaternary ammonium (QA) ions on potassium channels in squid axons. The study found that several QA ions cause inactivation of potassium conductance (gK), a phenomenon not typically observed in squid axons. The inactivation is characterized by an initial increase in gK followed by a spontaneous decrease to a fraction of its peak value, even when the depolarization is maintained. The mechanism of this inactivation involves: 1. QA ions only enter gK channels when the activation gates are open. 2. The activation gates of QA-occluded channels do not close readily. 3. Hyperpolarization helps to clear QA ions from the channels. 4. Raising the external K+ concentration also aids in clearing QA ions from the channels. These observations suggest that K+ ions traverse the membrane through pores rather than through a carrier mechanism. The data indicate that a K+ pore has two distinct parts: a wide inner mouth that can accept hydrated or partially dehydrated K+ ions, and a narrower portion that can accept dehydrated K+ ions but not TEA+. The study concludes that the blocking site for QA ions is directly within the K+ channel, and the effects of hyperpolarization and external K+ concentration on dissociation rate cannot be explained by a simple carrier model.This paper investigates the effects of various quaternary ammonium (QA) ions on potassium channels in squid axons. The study found that several QA ions cause inactivation of potassium conductance (gK), a phenomenon not typically observed in squid axons. The inactivation is characterized by an initial increase in gK followed by a spontaneous decrease to a fraction of its peak value, even when the depolarization is maintained. The mechanism of this inactivation involves: 1. QA ions only enter gK channels when the activation gates are open. 2. The activation gates of QA-occluded channels do not close readily. 3. Hyperpolarization helps to clear QA ions from the channels. 4. Raising the external K+ concentration also aids in clearing QA ions from the channels. These observations suggest that K+ ions traverse the membrane through pores rather than through a carrier mechanism. The data indicate that a K+ pore has two distinct parts: a wide inner mouth that can accept hydrated or partially dehydrated K+ ions, and a narrower portion that can accept dehydrated K+ ions but not TEA+. The study concludes that the blocking site for QA ions is directly within the K+ channel, and the effects of hyperpolarization and external K+ concentration on dissociation rate cannot be explained by a simple carrier model.