Activation of the atrial KACh channel by the βγ subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates

被引:221
作者
Sui, JL [1 ]
Petit-Jacques, J [1 ]
Logothetis, DE [1 ]
机构
[1] CUNY Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY 10029 USA
关键词
G protein-gated K+ channel; phosphatidylinositol 4,5-bisphosphate;
D O I
10.1073/pnas.95.3.1307
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The beta gamma subunits of GTP-binding proteins (G(beta gamma)) activate the muscarinic K+ channel (K-ACh) in heart by direct binding to both of its component subunits. K-ACh channels can also be gated by internal Na+ ions. Both activation mechanisms show dependence on hydrolysis of intracellular ATP. We report that phosphatidylinositol 4,5-bisphosphate (PIP2) mimics the ATP effects and that depletion or block of PIP2 retards the stimulatory effects of G(beta gamma) subunits or Na+ ions on channel activity, effects that can be reversed by restoring PIP2. Thus, regulation of K-ACh channel activity may be crucially dependent on PIP2 and phosphatidylinositol signaling. These striking functional results are in agreement with in vitro biochemical studies on the PIP2 requirement for G(beta gamma) stimulation of G protein receptor kinase activity, thus implicating phosphatidylinositol phospholipids as a potential control point for G(beta gamma)-mediated signal transduction.
引用
收藏
页码:1307 / 1312
页数:6
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