A pH-sensitive yeast outward rectifier K+ channel with two pore domains and novel gating properties.
YORK is a newly cloned K+ channel from yeast. Unlike all other cloned K+ channels, it has two pore domains instead of one. It displays eight transmembrane segments arranged like a covalent assembly of a Shaker-type voltage-dependent K+ channel (without S4 transmembrane segments) with an inward rectifier K+ channel. When expressed in Xenopus oocytes, YORK does not pass inward currents; it conducts only K+-selective outward currents. However, the mechanism responsible for this strict outward rectification is unusual. Like inward rectifiers, its activation potential threshold closely follows the K+ equilibrium potential. Unlike inward rectifiers, the rectification is not due to a voltage-dependent Mg2+ block. The blocking element is probably intrinsic to the YORK protein itself. YORK activity is decreased at acidic internal pH, with a pKa of 6.5. Pharmacological and regulation properties were analyzed. Ba2+ ions and quinine block YORK currents through high and low affinity sites, while tetraethylammonium displays only one affinity for blocking. Activation of protein kinase C indirectly produces an increase of the current, while protein kinase A activation has no effect.
Lesage
F
F
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Guillemare
E
E
Fink
M
M
Duprat
F
F
Lazdunski
M
M
Romey
G
G
Barhanin
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D003001:Cloning, Molecular; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
D015221:Potassium Channels; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C095220:TOK1 protein, S cerevisiae