Fifty years of progress in ion channel research

Fifty years ago, ion channels were but a reasonable hypothesis. I outline some major steps in transforming this idea from a plausible description of the biological assemblies responsible for controlling passive ion transport across membranes to established fact. Important electrophysiological, biochemical, molecular biological, structural, and theoretical tools are discussed in the context of the transition from studying whole cell preparations, containing many channels, to investigating single channel behavior. Six channel families are exemplified: the model peptide, gramicidin, the acetylcholine receptor, and the sodium, potassium, calcium, and chloride channels. Some questions of current interest are posed.