TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure

A new human weakly inward rectifying K+ channel, TWIK-1, has been isolated, This channel is 336 amino acids long and has four transmembrane domains, Unlike other mammalian K+ channels, it contains two pore-forming regions called P domains, Genes encoding structural homologues are present in the genome of Caenorhabditis elegans, TWIK-1 currents expressed in Xenopus oocytes are time-independent and present a nearly linear I-V relationship that saturated for depolarizations positive to 0 mV in the presence of internal Mg2+, This inward rectification is abolished in the absence of internal Mg2+, TWIK-1 has a unitary conductance of 34 pS and a kinetic behaviour that is dependent on the membrane potential, In the presence of internal Mg2+, the mean open times are 0.3 and 1.9 ms at -80 and +80 mV, respectively, The channel activity is up-regulated by activation of protein kinase C and down-regulated by internal acidification, Both types of regulation are indirect, TWIK-1 channel activity is blocked by Ba2+ (IC50 = 100 mu M), quinine (IC50 = 50 mu M) and quinidine (IC50 = 95 mu M). This channel is of particular interest because its mRNA is widely distributed in human tissues, and is particularly abundant in brain and heart. TWIK-1 channels are probably involved in the control of background K+ membrane conductances.