Interaction of Tetraethylammonium Ion Derivatives with the Potassium Channels of Giant Axons

A number of compounds related to TEA⁺ (tetraethylammoniumion) were injected into squid axons and their effects on g_K (the potassium conductance) were determined. In most of these ions a quaternary nitrogen is surrounded by three ethyl groups and a fourth group that is very hydrophobic. Several of the ions cause inactivation of g_K, a type of ionic gating that is not normally seen in squid axon; i.e., after depolarization g_K increases and then spontaneously decreases to a small fraction of its peak value even though the depolarization is maintained. Observations on the mechanism of this gating show that (a) QA (quaternary ammonium) ions only enter K⁺ channels that have open activation gates (the normal permeability gates). (b) The activation gates of QA-occluded channels do not close readily. (c) Hyperpolarization helps to clear QA ions from the channels. (d) Raising the external K⁺ concentration also helps to clear QA ions from the channels. Observations (c) and (d) strongly suggest that K⁺ ions traverse the membrane by way of pores, and they cannot be explained by the usual type of 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⁺.