TWIK-2, an inactivating 2P domain K+ channel

We cloned human and rat TWIK-2 and expressed this novel 2P domain K+ channe l in transiently transfected COS cells. TWIK-2 is highly expressed in the g astrointestinal tract, the vasculature, and the immune system. Rat TWIK-2 c urrents are about 15 times larger than human TWIK-2 currents, but both exhi bit outward rectification in a physiological K+ gradient and mild inward re ctification in symmetrical K+ conditions. TWIK-2 currents are inactivating at depolarized potentials, and the kinetic of inactivation is highly temper ature-sensitive. TWIK-2 shows an extremely low conductance, which prevents the visualization of discrete single channel events. The inactivation and r ectification are intrinsic properties of TWIK-2 channels. In a physiologica l K+ gradient, TWIK-2 is half inhibited by 0.1 mM Ba2+, quinine, and quinid ine, Finally, cysteine 53 in the M1P1 external loop is required for functio nal expression of TWIK-2 but is not critical for subunit self-assembly. TWI K-2 is the first reported 2P domain K+ channel that inactivates. The base-l ine, transient, and delayed activities of TWIK-2 suggest that this novel 2P domain K+ channel may play an important functional role in cell electrogen esis.