Asymmetric block of a monovalent cation-selective channel of rabbit cardiac sarcoplasmic reticulum by succinyl choline

Abstract

We have investigated the effect of the skeletal muscle relaxant succinyl choline (SC) on the conduction of potassium ions through a monovalent cation-selective channel present in the cardiac muscle sarcoplasmic reticulum membrane (CSR). This channel has been studied under voltage-clamp conditions following the fusion of purified CSR membrane vesicles with preformed planar phospholipid bilayers. The channel assumes a fixed orientation in the bilayer and displays two conducting states (B. Tomlins, A.J. Williams & R.A.P. Montgomery, 1984, J. Membrane Biol. 80:191-199). SC blocks potassium conductance through the channel in a voltage-dependent manner. Block occurs from both sides of the channel, in both conducting states and is resolved as discrete "flickering" events. Although SC is capable of blocking potassium conductance from both sides of the membrane, block is asymmetric. The zero-voltage dissociation constant for block from the cis side of the membrane is approximately threefold lower than that from the trans side. Block from the cis side displays a linear dependence on SC concentration for both open states and is competitive with potassium ions at saturating potassium activities, consistent with a single-site blocking model. The degree of SC-induced block is also influenced by membrane surface charge. SC block differs from that previously described for bis quaternary ammonium (bis Qn) compounds such as decamethonium in that SC blocks preferentially from the cis side of the channel.