Surfing the DNA databases for K+ channels nets yet more diversity

Abstract

Lawrence Salkoff*t and Timothy Jegla* * Department of Anatomy and Neurobiology tDepartment of Genetics Washington University School of Medicine St. Louis, Missouri 63110 K ÷ channels are a life and death matter. Perhaps the best assessment of whether a cell is living or dead is whether or not it has a membrane potential, and K ÷ channels have a significant role in setting the membrane potential in cells from a wide variety of life forms. In addition to this life or death matter, K ÷ channels serve a host of other functions relating to the electrical lives of cells, like setting the fre- quency and duration of action potentials and, in general, shaping the electrical activity of cells. Because multiple K ÷ channel types have also been found in a wide variety of cells that are not known to be electrically excitable, it is likely that we don't yet comprehend all of the functions of these versatile proteins. It's not unexpected then that the burgeoning data from various genome sequencing projects is revealing the prevalence and diversity of K ÷ channels in virtually every major class of organism. In- deed, data now surfacing from the various genomic DNA sequencing projects suggest that this family of proteins might be even more diverse than previously imagined. With the publication of the TOK1 channel primary structure and expression data by Ketchum et al. (1995), we get the first glimpse of a K ÷ channel from yeast, a unicellular fun- gus. The TOK1 channel is novel, not only because of its unique subunit structure (it resembles two K ÷ channel sub- units of different classes linked together) and its unique physiology (it is outwardly rectifying by a nonconventional mechanism), but also because of the way in which this unique channel was found. Rather than using the conven- tional experimental methods of molecular biology in a wet lab, the authors discovered TOK1 by surfing the public DNA database for one of the rare and special ancient con- served protein regions that have been identified as a result of the genome sequencing projects (Green et al., 1993). This particular ancient conserved region is the universal signature of the ion-selective pore of K ÷ channels. The existence of K ÷ channels in yeast was discovered almost a decade ago by physiological recordings (Gustin et al., 1986). The current revelation of their structure and their relation to K ÷ channels in other organisms is a good exam- ple of how genome sequencing projects have accelerated the pace of discovery in biology.