An ion's view of the potassium channel. The structure of the permeation pathway as sensed by a variety of blocking ions.

Abstract

The block of K channels [nerve membrane] was studied in voltage-clamped squid giant axons by 9 organic and alkali cations, in order to learn how the channel selects among entering ions. When added to the internal solution, all of the ions blocked the channels, with inside-positive voltages enhancing the block. Cs blocked the channels from the outside as well, with inside-negative voltages favoring block. The depths to which different ions entered the channel were compared by estimating the "apparent electrical distance" to the blocking site. Simulations with a 3-barrier, double-occupany model showed that the "apparent electrical distance," expressed as a fraction of the total transmembrane voltage, appeared to be less than the actual value if the blocking ion passed completely through the channel. Na and Cs apparently block at sites further into the channel than those occupied by Li and the organic blockers. The depth to which an ion readily penetrates into the K channel depends on its size and on the specific chemical groups on its molecular surface. The additon of hydroxyl groups to alkyl chains on a quaternary ammonium ion decreases the strength of binding and allows deeper penetration into the channel. For alkali cations, the degree of hydration is probably crucial in determining how far an ion penetrates. Li the most strongly hydrated, appeared not to penetrate as far as Na and Cs. There are, minimally, 4 ion binding sites in the permeation pathway of the K channel, with simultaneous occupancy of at least 2.