Sci. STKE, 6 August 2002
Channels PI(4,5)P2 Required for Recovery
The M current (IM) is a potassium current that is inhibited by certain classes of G protein-coupled receptors (those that can activate Gq/11), leading to increased neuronal excitability. Suh and Hille showed that hydrolysis of adenosine triphosphate (ATP) was required for the recovery of inhibition of IM following activation of muscarinic acetylcholine receptors in both a heterologous expression system and in sympathetic neurons. Agents that inhibited phosphatidylinositol 4-kinase (PI4K) blocked the recovery of IM following muscarinic receptor activation. Thus, the activation of the G protein-coupled receptor stimulates Gq/11, which activates phopholipase C, thereby hydrolyzing PI(4,5)P2. This decrease in PI(4,5)P2 contributes to inhibition of IM, and the action of PI4K is responsible for the resynthesis of PI(4,5)P2, which allows the channel to recover from inhibition. For more on membrane proteins regulated by changes in PI(4,5)P2, see Hilgemann.
B.-C. Suh, B. HIlle, Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphophonate synthesis. Neuron 35, 507-520 (2002). [Online Journal]
D. W. Hilgemann, S. Feng, C. Nasuhoglu, The complex and intriguing lives of PIP2 with ion channels and transporters. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/111/re19 [Abstract] [Full Text]
Citation: PI(4,5)P2 Required for Recovery. Sci. STKE 2002, tw284 (2002).
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