Structural aspects of the sarcoplasmic reticulum K+ channel revealed by gallamine block.
We have studied single-channel conductance fluctuations of K+ channels present in the sarcoplasmic reticulum (SR) membrane systems of rabbit cardiac and skeletal muscle. K+ conductance through the channels is reversibly blocked by gallamine. Conductance block occurs only from the trans side of the channel and is resolved as a smooth reduction in the open state conductance. At a fixed K+ concentration, conduction decreases with increasing gallamine concentration and the data can be fitted to a single-site inhibition scheme. The degree of block seen at a constant gallamine concentration decreases as K+ concentration is increased, indicating competition between gallamine and K+. Gallamine block is voltage dependent, the degree of block increasing with increasing negative holding potential. Quantitative analysis of block yields a zero voltage dissociation constant of 55.3 +/- 16 microM and an effective valence of block of 0.93 +/- 0.12. We conclude that gallamine blocks by interacting with a site or sites located at an electrical distance 30-35% into the voltage drop from the trans side of the channel. This site must have a cross-sectional area of at least 1.2 nm2. The results of this study have been used to modify and extend our view of the structure of the channel's conduction pathway.
Gray
M A
MA
Department of Cardiac Medicine, University of London, United Kingdom.
Tomlins
B
B
Montgomery
R A
RA
Williams
A J
AJ
D000818:Animals; D004553:Electric Conductivity; D005703:Gallamine Triethiodide / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009132:Muscles / Q000502:physiology; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D007473:Ion Channels; D005703:Gallamine Triethiodide; D011188:Potassium