Petit-Jacques J, Sui J L, Logothetis D E
Department of Physiology, Mount Sinai School of Medicine of the New York University, New York, New York 10029, USA.
J Gen Physiol. 1999 Nov;114(5):673-84. doi: 10.1085/jgp.114.5.673.
Native and recombinant G protein-gated inwardly rectifying potassium (GIRK) channels are directly activated by the betagamma subunits of GTP-binding (G) proteins. The presence of phosphatidylinositol-bis-phosphate (PIP(2)) is required for G protein activation. Formation (via hydrolysis of ATP) of endogenous PIP(2) or application of exogenous PIP(2) increases the mean open time of GIRK channels and sensitizes them to gating by internal Na(+) ions. In the present study, we show that the activity of ATP- or PIP(2)-modified channels could also be stimulated by intracellular Mg(2+) ions. In addition, Mg(2+) ions reduced the single-channel conductance of GIRK channels, independently of their gating ability. Both Na(+) and Mg(2+) ions exert their gating effects independently of each other or of the activation by the G(betagamma) subunits. At high levels of PIP(2), synergistic interactions among Na(+), Mg(2+), and G(betagamma) subunits resulted in severalfold stimulated levels of channel activity. Changes in ionic concentrations and/or G protein subunits in the local environment of these K(+) channels could provide a rapid amplification mechanism for generation of graded activity, thereby adjusting the level of excitability of the cells.
天然和重组的G蛋白门控内向整流钾通道（GIRK通道）直接由GTP结合蛋白（G蛋白）的βγ亚基激活。G蛋白激活需要磷脂酰肌醇二磷酸（PIP₂）的存在。内源性PIP₂的形成（通过ATP水解）或外源性PIP₂的应用增加了GIRK通道的平均开放时间，并使它们对内部钠离子的门控更敏感。在本研究中，我们表明ATP或PIP₂修饰通道的活性也可被细胞内镁离子刺激。此外，镁离子降低了GIRK通道的单通道电导，这与其门控能力无关。钠离子和镁离子彼此独立地或与Gβγ亚基的激活无关地发挥它们的门控作用。在高水平的PIP₂时，钠离子、镁离子和Gβγ亚基之间的协同相互作用导致通道活性水平提高了几倍。这些钾通道局部环境中离子浓度和/或G蛋白亚基的变化可为分级活性生成提供快速放大机制，从而调节细胞的兴奋性水平。
