A contribution to the history of the proton channel.

The low numbers of hydrogen ions in physiological solutions encouraged the assumption that H(+) currents flowing through conductive pathways would be so small as to be unmeasurable even if theoretically possible. Evidence for an H(+)-based action potential in the luminescent dinoflagellate Noctiluca and for an H(+)-conducting channel created by the secretions of the bacterium Bacillus brevis, did little to alter this perception. The clear demonstration of H(+) conduction in molluscan neurons might have provided the breakthrough but the new pathway was without an easily demonstrable function, and escaped general attention. Indeed the extreme measures that must be taken to successfully isolate H(+) currents meant that it was some years before proton channels were identified in mammalian cells. However, with the general availability of patch-clamp techniques and evidence for an important role in mammalian neutrophils, the stage was set for a series of structure/function studies with the potential to make the proton channel the best understood channel of all. In addition, widespread genomic searches have established that proton channels play important roles in processes ranging from fertilization of the human ovum to the progression of breast cancer. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.