Mechanisms of Cs+ blockade in a Ca2+-activated K+ channel from smooth muscle.
Large unitary conductance Ca2+-activated K+ channels from smooth muscle membrane were incorporated into phospholipid planar bilayers, and the blockade induced by internally and externally applied Cs+ was characterized. Internal Cs+ blockade is voltage dependent and can be explained on the basis of a Cs+ binding to a site that senses 54% of the applied voltage, with an apparent dissociation constant, Kd(0), of 70 mM. On the other hand, external Cs+ blocks the channel in micromolar amounts, and the voltage dependence of blockade is a function of Cs+ concentration. The fractional electrical distance can be as large as 1.4 at 10 mM Cs+. This last result suggests that the channel behaves as a multi-ion pore. At large negative voltages the I-V relationships in the presence of external Cs+ show an upturn, indicating relief of Cs+ block. External Cs+ blockade is relieved by increasing the internal K+ concentration, but can be enhanced by increasing the external K+. All the characteristics of external Cs+ block can be explained by a model that incorporates a "knock-on" of Cs+ by K+.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002586:Cesium / Q000494:pharmacology*; D004553:Electric Conductivity; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008051:Lipid Bilayers; D008954:Models, Biological; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010714:Phosphatidylethanolamines; D011188:Potassium / Q000378:metabolism; D011817:Rabbits
D007473:Ion Channels; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D002586:Cesium; D011188:Potassium; D002118:Calcium