With the sequencing of the human genome it turned out that many of the genetically identified genes have an unknown function and one of the major problems of biology is the “annotation” of the genome. But the reverse problem persists, i.e., that for many functionally well-defined proteins the coding gene has not been identified. This reverse problem is difficult to tackle because the molecular tools that help for the annotation (for example knock-out, heterologous expression, localization) cannot be applied. For ion channels in particular, biochemical approaches are also hampered by the low protein abundance. These are well-known problems for two different classes of Cl ion channels: “swelling”-activated and Ca2+-activated channels. The latter type of Cl channel is involved in epithelial salt transport, in the regulation of the membrane potential of smooth and heart muscle cells, in the block of polyspermi in...

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