VOLTAGE-GATED CATION CONDUCTANCE CHANNEL FROM FRAGMENTED SARCOPLASMIC-RETICULUM - EFFECTS OF TRANSITION-METAL IONS

The effects of transition metal ions on the voltage-gated K+ conductance of a channel-type ionophore from sarcoplasmic reticulum membranes have been studied in an artificial planar bilayer system. Channels are inserted into the planar bilayer by a process resembling fusion with sarcoplasmic reticulum vesicles. K+ conductance is modulated by transition metal ions in two ways. First, the conductance is irreversibly inhibited by certain ions added on either side of the membrane. The inhibition rate constants are ordered: [Formula Omitted] mersalyl. Mn2+, Co2+, and Ni2+ are inactive. The rate constant of inhibition by mersalyl is voltage dependent. Second, certain ions cause a reversible three- to fourfold stimulation of the K+ conductance; the effect is seen only when the transition metal ion is added to the side of the membrane opposite to the side containing sarcoplasmic reticulum vesicles. The affinity constants for this stimulation fall in the order: [Formula Omitted] Organomercurials, Hg2+, and Ag+ fail to give this trans stimulation effect. These effects are seen only on the monovalent cation conductance channel, not on the anion conductance pathway, which can be assayed under different conditions. Neither effect is given by alkaline-earth cations. Single-channel fluctuation experiments demonstrate that the trans stimulation is an effect upon the probability of the channel's opening rather than on the conductance of the open channel. The possibility of a sulfhydryl group's involvement in the active channel is raised, and a simple model for the channel is presented. © 1979, American Chemical Society. All rights reserved.