CHANNELS PI(4,5)P₂ Required for Recovery

The M current (I_M) is a potassium current that is inhibited by certain classes of G protein-coupled receptors (those that can activate G_q/11), leading to increased neuronal excitability. Suh and Hille showed that hydrolysis of adenosine triphosphate (ATP) was required for the recovery of inhibition of I_M 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 I_M following muscarinic receptor activation. Thus, the activation of the G protein-coupled receptor stimulates G_q/11, which activates phopholipase C, thereby hydrolyzing PI(4,5)P₂. This decrease in PI(4,5)P₂ contributes to inhibition of I_M, 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]

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The Complex and Intriguing Lives of PIP₂ with Ion Channels and Transporters

Donald W. Hilgemann, Siyi Feng, and Cem Nasuhoglu (4 December 2001)
Sci. STKE 2001 (111), re19. [DOI: 10.1126/stke.2001.111.re19]
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