Conduction and block by organic cations in a K+-selective channel from sarcoplasmic reticulum incorporated into planar phospholipid bilayers.

Abstract

A collection of organic cations was used to probe the gross structural features of the ionic diffusion pathway in a K+-selective channel from [mammalian] sarcoplasmic reticulum (SR). Channels were incorporated into planar phospholipid bilayer membranes, and single-channel currents were measured in the presence of NH4--derived cations in the aqueous phases. Small monovalent organic cations are able to permeate the channel: the channel conductance drops sharply for cations having molecular cross sections larger than 18-20 .ANG.2. Impermeant or poorly permeant cations such as tetraethylammonium, choline and glucosamine, among others, block K+ conduction through the channel. This block is voltage dependent and can be described by a 1-site, 1-ion blocking scheme. Nineteen monovalent organic cations block primarily from the trans side of the membrane (the side defined as 0 voltage), and much more weakly, if at all, from the cis side (to which SR vesicles are added). These blockers all appear to interact with a site located at 63% (average value) of the electric potential drop measured from the tran side. Block by 1,3-bis[tris(hydroxymethyl)-methylamino]propane (BTP) shows that the presence of a blocking ion increases the duration of the apparent open state, as expected for a scheme in which the blocking site can be reached only when the channel is open. The results lead to a picture of the channel containing a wide (at least 50 .ANG.2) nonselective trans entry in series with a narrow (20 .ANG.2) constriction.