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

@article{citeulike:406606, 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.}, address = {Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.}, author = {Zhang, H. and Craciun, L. C. and Mirshahi, T. and Rohacs, T. and Lopes, C. M. and Jin, T. and Logothetis, D. E.}, citeulike-article-id = {406606}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/12670425}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=12670425}, day = {27}, issn = {0896-6273}, journal = {Neuron}, keywords = {1-phosphatidylinositol, amp, androstadiene, channel, cho, conductivity, enzyme, hydrolysis, inhibition, inhibitor, kcnq, laevis, m1, microscopy, muscarinic, mutation, neurons, phosphatidylinositol, pip2, receptor, tea, transduction}, month = {March}, number = {6}, pages = {963--975}, posted-at = {2005-11-23 19:41:19}, priority = {2}, title = {PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12670425}, volume = {37}, year = {2003} }

TY - JOUR ID - citeulike:406606 L3 - citeulike-article-id:406606 N2 - 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. IS - 6 JF - Neuron SN - 0896-6273 AD - Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA. EP - 975 TI - PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents. VL - 37 SP - 963 KW - 1-phosphatidylinositol KW - amp KW - androstadiene KW - channel KW - cho KW - conductivity KW - enzyme KW - hydrolysis KW - inhibition KW - inhibitor KW - kcnq KW - laevis KW - m1 KW - microscopy KW - muscarinic KW - mutation KW - neurons KW - phosphatidylinositol KW - pip2 KW - receptor KW - tea KW - transduction AU - Zhang, H AU - Craciun, LC AU - Mirshahi, T AU - Rohacs, T AU - Lopes, CM AU - Jin, T AU - Logothetis, DE PY - 2003/03/27/ UR - http://view.ncbi.nlm.nih.gov/pubmed/12670425 ER -