Decamethonium and hexamethonium block K⁺ channels of sarcoplasmic reticulum

Abstract

The sarcoplasmic reticulum membrane (SR) of skeletal muscle contains cation-selective channels which have been detected by isotope fluxes in fragmented SR vesicles¹, fluorimetric dyes² and direct incorporation of SR vesicles to planar phospholipid bilayers^3–5. SR channels incorporated in bilayers have a single open-state conductance of 140 pS in 0.1 M K⁺ (refs 4, 5). We have previously reported blockade of the SR channel by Cs⁺, a low-affinity blocker with a zero-voltage dissociation constant of 40 mM (ref. 6). We showed that increasing Cs⁺ concentrations reduced the open-channel conductance, increased the mean open time and conferred voltage dependence on the open-state conductance⁶. Here we report on the blockade induced by the cholinergic drugs decamethonium and hexamethonium⁷ on the SR channel. Although blockade by hexamethonium is similar to that of Cs⁺, decamethonium blocks with a much higher affinity and induces flickering events which are probably due to the interaction of single drug molecules with the open state.