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

1998; National Academy of Sciences; Volume: 95; Issue: 3 Linguagem: Inglês

10.1073/pnas.95.3.1307

1091-6490

Jin Sui, Jérôme Petit-Jacques, Diomedes E. Logothetis,

Receptor Mechanisms and Signaling

The βγ subunits of GTP-binding proteins (G βγ ) 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 (PIP 2 ) mimics the ATP effects and that depletion or block of PIP 2 retards the stimulatory effects of G βγ subunits or Na + ions on channel activity, effects that can be reversed by restoring PIP 2 . Thus, regulation of K ACh channel activity may be crucially dependent on PIP 2 and phosphatidylinositol signaling. These striking functional results are in agreement with in vitro biochemical studies on the PIP 2 requirement for G βγ stimulation of G protein receptor kinase activity, thus implicating phosphatidylinositol phospholipids as a potential control point for G βγ -mediated signal transduction.