With the sequencing and annotation of multiple genomes now complete, it is possible to survey whole families of genes at once in silico. One of the more remarkable findings is the sheer size of the potassium channel family– or families, because they are also remarkably diverse. This is in contrast to the channel families for the other major ions (sodium, chloride and calcium), each of which only have a few dozen representatives.
Why then are there so many potassium channels? In this paper, we begin to get an inkling. Salkoff and a large team of collaborators use reverse genetic techniques to dissect the potassium channels in the body wall muscle of the genetic model worm Caenorhabditis elegans. This may not seem like a smart choice for physiology, when the whole organism is only a millimeter long and has only a thousand cells! Nonetheless, there are several advantages. Firstly, each worm conforms to an invariant developmental plan, so every cell in the organism is known, and its cell lineage mapped. This allows `identified cell' physiology; repeat experiments can be performed on the identical cell(rather than similar cells) in multiple individuals, so reducing experimental variability. Secondly, the genome is sequenced, so all potential genes (in this case, for the >70 potassium channels) are already known. Thirdly, the experimenters already knew, from systematic studies with worms transgenic for green fluorescent protein fused to promoters for different potassium channel genes, that only nine genes were likely to be of interest to them, with detectable expression in muscle. Fourthly, there is a wealth of existing mutants for various genes. And fifthly, it is possible to knock down the activity of individual genes by RNA interference, a technique that works nowhere better than in C. elegans. In fact, it is necessary merely to feed the worms with E. coli bacteria expressing RNAi from plasmids,and there are systematic panels of such E. coli freely available.
Using these techniques, it was possible to show that, of the channels known to be expressed in muscle, only SHAL and SHAKER normally carried significant current. So what were the others there for? The authors' answer is based on a single channel, SLO-2. This is normally not functional under physiological conditions. However, when the worm is exposed to hypoxic conditions (something that could be expected to happen frequently in the worm's natural soil-living habitat), the SLO-2 channel becomes the major potassium carrier in the muscle. The authors' plausible hypothesis is thus that the other, `reserve', channels are also present to be invoked under different, exceptional physiological conditions, and that this conveys a sufficient selective advantage to justify the organism's investment in making channel proteins that are not normally used. Consistent with this, slo mutants are known to be hypersensitive to hypoxia. By extension, this argument can be extended to other gene families and to other organisms.