Starring TREK-1

Abstract

See related article, pages 176–184 “We are more alike than unlike, my dear Captain. I have pores, humans have pores.” Lieutenant Commander Data, Stardate 41209.2 Before 1996, all known mammalian K+ channels were classified into only two different structural families according to the number of transmembrane (TM) spanning and pore-forming (P) domains in their α subunit. One family is characterized by K+ channels composed of two TM domains and one P domain, and includes the inwardly rectifying and ATP-sensitive K+ channels. The second family represents K+ channels characterized by six or seven TM domains and one P domain, and includes the voltage-gated and Ca2+-activated K+ channels. To form one functional channel for either of these families, four α subunits assemble to establish one K+ permeable pore. In the mid 1990s, researchers took advantage of the fact that the P domain of each K+ channel’s pore-forming α subunit is highly conserved across species and represents a common structural motif.1 Genome searches for DNA sequences coding for the P domain revealed a unique K+ channel in yeast and Caenorhabditis elegans that contained two P domains within a single α subunit polypeptide having eight potential TM domains.2 The following year a human K+ channel was cloned that also showed the unique feature of two P domains, but displayed four TM domains in a single α subunit (Figure 1).3 The channel was given the name TWIK-1 ( T andem of P domains in a W eak I nward rectifying K + channel). Since the cloning of TWIK-1, a total of fifteen …