Possible Interaction: Adenosine Triphosphate and Phosphatidylinositol 4,5-Diphosphate

“Conversely, channel opening is potentiated by phosphoinositol bisphosphate PIP2 ), which binds to Kir6.2 and reduces channel inhibition by ATP.”

“Our model suggests how PIP2 increases channel opening and decreases ATP binding and channel inhibition.”

“How does PIP2 reduce the sensitivity of the channel to ATP?”

“There were synergic effects between ATP and GTP, ATP and PIP2 , but not between ATP and GTPγ[S] , or PIP2 and GTPγ[S].”

“However, in both cases, PIP2 reversed the increase in ATP sensitivity, indicating that PIP2 lowers the ATP sensitivity by increasing P o as well as by decreasing the channel affinity for ATP.”

“Reduction of membrane phosphatidylinositol 4,5-biphosphate (PIP2) content by adenosine triphosphate depletion or activation of phosphoinositidase C resulted in a decrease in band 4.1 binding capacity to a similar extent in both control and Leach vesicles.”

“Addition of guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) significantly stimulated hydrolysis of PIP2 , but not PI.”

“Stimulation of PIP2 hydrolysis by GTP was dose-dependent between 1-100 microM GTP.”

“ ATP dose- dependently stimulated PIP2 synthesis with half-maximal effect at 300 μmol/l.”

“PIP2 was resynthesized with a half-time of ∼50 s. When PIP2 resynthesis was prevented by depriving the cell of ATP , the Kir current spontaneously decayed at maximal rates representing a loss of ∼40% loss of total PIP2 per minute.”

“Here, we show that the stimulatory effect of ATP and GTPγS on clathrin coat recruitment is mediated at least in part by increased levels of PIP2.”

“Applying phosphatidylinositol 4,5‐bisphosphate (PIP2) to inside‐out patches in place of ATP also increased GIRK activity; however, only an increase in the frequency of opening was observed.”

“Following maximal activation by PIP2, ATP caused an additional 2.2‐fold increase in GIRK activity.”