The study investigates the interaction of quaternary ammonium (QA) ions with potassium (K⁺) channels in squid giant axons. TEA⁺ and other QA ions were injected into axons, and their effects on potassium conductance (gₖ) were analyzed. These ions cause inactivation of gₖ, a type of ionic gating not normally seen in squid axons. Observations suggest that QA ions enter only open K⁺ channels and are cleared by hyperpolarization or increased external K⁺ concentration. These findings indicate that K⁺ ions traverse the membrane through pores rather than via a carrier model. The data suggest that a K⁺ pore has two distinct parts: a wide inner mouth that can accept a hydrated K⁺ ion or a TEA⁺-like ion, and a narrower portion that can accept a dehydrated or partially dehydrated K⁺ ion but not TEA⁺. The study also shows that QA ions can enter the blocking sites of K⁺ channels only when the activation gates are open. The inactivation of gₖ is influenced by the hydrophobicity of the QA ion's side chain, with more hydrophobic ions binding more tightly to the blocking sites. The recovery from inactivation depends on factors such as the QA ion concentration, membrane potential, and external K⁺ concentration. The results support the idea that K⁺ ions move through pores rather than via a carrier mechanism, and that the blocking site is directly in the K⁺ channel. The study concludes that the potassium channels have a complex gating mechanism involving activation and inactivation gates, and that the interaction of QA ions with these channels provides insights into the mechanism of ion permeation through the membrane.The study investigates the interaction of quaternary ammonium (QA) ions with potassium (K⁺) channels in squid giant axons. TEA⁺ and other QA ions were injected into axons, and their effects on potassium conductance (gₖ) were analyzed. These ions cause inactivation of gₖ, a type of ionic gating not normally seen in squid axons. Observations suggest that QA ions enter only open K⁺ channels and are cleared by hyperpolarization or increased external K⁺ concentration. These findings indicate that K⁺ ions traverse the membrane through pores rather than via a carrier model. The data suggest that a K⁺ pore has two distinct parts: a wide inner mouth that can accept a hydrated K⁺ ion or a TEA⁺-like ion, and a narrower portion that can accept a dehydrated or partially dehydrated K⁺ ion but not TEA⁺. The study also shows that QA ions can enter the blocking sites of K⁺ channels only when the activation gates are open. The inactivation of gₖ is influenced by the hydrophobicity of the QA ion's side chain, with more hydrophobic ions binding more tightly to the blocking sites. The recovery from inactivation depends on factors such as the QA ion concentration, membrane potential, and external K⁺ concentration. The results support the idea that K⁺ ions move through pores rather than via a carrier mechanism, and that the blocking site is directly in the K⁺ channel. The study concludes that the potassium channels have a complex gating mechanism involving activation and inactivation gates, and that the interaction of QA ions with these channels provides insights into the mechanism of ion permeation through the membrane.