Opening the Shaker K channel should be easy. Release the membrane potential that normally holds it closed, and massive stored molecular energies snap it rapidly and inexorably into its open configuration. Unlocking the inner secrets of this voltage-dependent channel's gating mechanism has proven to be much more difficult. An article by Ledwell and Aldrich in this issue has opened that door significantly.
An impressive array of experimental techniques and intellectual powers have been used to attack this problem over the past half century. Techniques such as the voltage clamp for measuring macroscopic and gating currents, and the patch clamp for small cells and single channels were developed to study voltage-dependent channels. Molecular cloning and mutagenesis, cysteine-site availability, limiting slope measurements, fluorescence labeling, rescue mutations, as well as temperature, pressure, water, and ionic alterations have all been brought to bear on the problem. An acceleration of progress is apparent through...
