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 Ba(2+), 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.
Patel
A J
AJ
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Maingret
F
F
Magnone
V
V
Fosset
M
M
Lazdunski
M
M
Honoré
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001464:Barium / Q000494:pharmacology; D019556:COS Cells; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D013696:Temperature; D014162:Transfection
C118290:KCNK6 protein, human; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011994:Recombinant Proteins; D001464:Barium; D008274:Magnesium