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XB-ART-5507
Neuron. March 27, 2003; 37 (6): 963-75.

PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.

Zhang H , Craciun LC , Mirshahi T , Rohács T , Lopes CM , Jin T , Logothetis DE .


Abstract
KCNQ channels belong to a family of potassium ion channels with crucial roles in physiology and disease. Heteromers of KCNQ2/3 subunits constitute the neuronal M channels. Inhibition of M currents, by pathways that stimulate phospholipase C activity, controls excitability throughout the nervous system. Here we show that a common feature of all KCNQ channels is their activation by the signaling membrane phospholipid phosphatidylinositol-bis-phosphate (PIP(2)). We show that wortmannin, at concentrations that prevent recovery from receptor-mediated inhibition of M currents, blocks PIP(2) replenishment to the cell surface. Moreover, we identify a C-terminal histidine residue, immediately proximal to the plasma membrane, mutation of which renders M channels less sensitive to PIP(2) and more sensitive to receptor-mediated inhibition. Finally, native or recombinant channels inhibited by muscarinic agonists can be activated by PIP(2). Our data strongly suggest that PIP(2) acts as a membrane-diffusible second messenger to regulate directly the activity of KCNQ currents.

PubMed ID: 12670425
Article link: Neuron.
Grant support: GM20856 NIGMS NIH HHS , HL-59949 NHLBI NIH HHS , HL-59949 NHLBI NIH HHS , HL-59949 NHLBI NIH HHS , HL-59949 NHLBI NIH HHS , HL-59949 NHLBI NIH HHS , HL-59949 NHLBI NIH HHS , HL10307 NHLBI NIH HHS , HL10307 NHLBI NIH HHS , HL10307 NHLBI NIH HHS , HL10307 NHLBI NIH HHS , HL10307 NHLBI NIH HHS , HL10307 NHLBI NIH HHS

Genes referenced: kcnq2
Antibodies referenced:
Morpholinos referenced:

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