K+ channels are divided into three subclasses, reflecting the number of transmembrane segments (TMS), which are designated 6TMS, 4TMS and 2TMS. Members of the 4TMS class contain two distinct pore regions, and include TASK, TREK, TRAAK and TWIK. TWIK-1 mRNA is expressed abundantly in brain and at lower levels in lung, kidney and skeletal muscle. The molecular weight of TWIK-1 in mouse brain is 40 kDa under reducing conditions. TWIK-2 shares low sequence homology with other mammalian family group members, and only 34% homology with TWIK-1. Human TWIK-2 is expressed in pancreas, placenta and heart, while mouse TWIK-2 is expressed in liver. TWIK-2 is inhibited by intracellular, but not extracellular, acidification.