Inactivation of monazomycin-induced voltage-dependent conductance in thin lipid membranes. II. Inactivation produced by monazomycin transport through the membrane.

Abstract

At sufficiently large conductances, the voltage-dependent conductance induced in thin lipid membranes by monazomycin undergoes inactivation. This is a consequence of depletion of monazomycin from the membrane:solution interface, as monazomycin crosses the membrane to the opposite (trans) side from which it was added. The flux of monazomycin is directly proportional to the monazomycin-induced conductance; at a given conductance it is independent of monazomycin concentration. When monazomycin channels break up, some or all of the molecules making up a channel are probably deposited on the trans side. A model is presented for the monazomycin channel: approximately 5 molecules, each spanning the membrane with its NH3+ on the trans side and an uncharged hydrophilic (probably sugar) group anchored to the cis side, form an aqueous channel lined by -OH groups. The voltage dependence arises from the flipping by the electrical field of molecules lying parallel to the cis surface into the "spanned state"; the subsequent aggregation of these molecules into channels is, to a first approximation, voltage independent. The channel breakup that deposits monomers on the trans side involves the collapsing of the channel in such a way that the uncharged hydrophilic groups remain in contact with the water in the channel as they close the channel from behind. The possibility that inactivation of Na+ channels in nerve involves the movement from one side of the membrane to the other of the molecules (or molecule) forming the channel is discussed.