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

We cloned human and rat TWIK-2 and expressed this novel 2P domain K+ channel in transiently transfected COS cells. TWIK-2 is highly expressed in the gastrointestinal tract, the vasculature, and the immune system. Rat TWIK-2 currents are about 15 times larger than human TWIK-2 currents, but both exhibit outward rectification in a physiological K+ gradient and mild inward rectification in symmetrical K+ conditions. TWIK-2 currents are inactivating at depolarized potentials, and the kinetic of inactivation is highly temperature-sensitive. TWIK-2 shows an extremely low conductance, which prevents the visualization of discrete single channel events. The inactivation and rectification are intrinsic properties of TWIK-2 channels. In a physiological K+ gradient, TWIK-2 is half inhibited by 0.1 mM Ba2+, quinine, and quinidine, Finally, cysteine 53 in the M1P1 external loop is required for functional expression of TWIK-2 but is not critical for subunit self-assembly. TWIK-2 is the first reported 2P domain K+ channel that inactivates. The base-line, transient, and delayed activities of TWIK-2 suggest that this novel 2P domain K+ channel may play an important functional role in cell electrogenesis.