Guanidine block of single channel currents activated by acetylcholine.
The acetylcholine-activated channel of chick myotube was studied using the patch-clamp method. Single channel current amplitudes were measured between -300 and +250 mV in solutions containing the permeant ions Cs+ and guanidine (G+). G+ has a relative permeability, PG/PCs, of 1.6, but carries no more than half the current that Cs+ does, with an equivalent electrochemical driving force. Experiments using G+ revealed an asymmetry of the acetylcholine-activated channel, with G+ being more effective at reducing Cs+ currents when added to the outside than when added to the inside. The block caused by outside, but not inside, G+ was evident for both inward and outward currents. The block caused by outside G+ was voltage dependent, first increasing and then being partially relieved when the driving force was made more negative. Experiments with mixtures of Cs+ and G+ revealed anomalously low magnitudes for reversal potentials, relative to predictions based on the Goldman-Hodgkin-Katz equation. These findings are consistent with a two-well, three-barrier Eyring rate model for ion flow, and demonstrate that a highly permeant ion, guanidine, can block asymmetrically by acting from within the voltage field of the acetylcholine-activated channel.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D004553:Electric Conductivity; D004594:Electrophysiology; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D007477:Ions
D006146:Guanidines; D007473:Ion Channels; D007477:Ions; D019791:Guanidine; D000109:Acetylcholine