Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
J Biol Chem. 1996 Feb 23;271(8):4183-7. doi: 10.1074/jbc.271.8.4183.
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.
YORK是一种新克隆的来自酵母的钾离子通道。与所有其他克隆的钾离子通道不同，它有两个孔结构域而非一个。它呈现出八个跨膜片段，其排列方式类似于一个与内向整流钾离子通道共价组装的Shaker型电压依赖性钾离子通道（没有S4跨膜片段）。当在非洲爪蟾卵母细胞中表达时，YORK不通过内向电流；它仅传导钾离子选择性外向电流。然而，导致这种严格外向整流的机制并不寻常。与内向整流器一样，其激活电位阈值紧密跟随钾离子平衡电位。与内向整流器不同的是，整流并非由于电压依赖性镁离子阻滞。阻滞元件可能是YORK蛋白本身所固有的。YORK活性在酸性胞内pH值下降低，其pKa为6.5。对其药理学和调节特性进行了分析。钡离子和奎宁通过高亲和力和低亲和力位点阻滞YORK电流，而四乙铵仅表现出一种阻滞亲和力。蛋白激酶C的激活间接导致电流增加，而蛋白激酶A的激活则没有影响。
