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• W2000702625 abstract "Voltage-gated Kv7 (KCNQ) channels underlie important K + currents, including the neuronal M current, and are thought to be sensitive to membrane phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and PIP 2 depletion to underlie muscarinic receptor inhibition. We studied regulation of Kv7.2-7.4 channels by PIP 2 in Chinese hamster ovary (CHO) cells using single-channel and whole-cell patch clamp and biochemical analysis. Maximal open probabilities ( P o ) of Kv7.2-Kv7.4 homomultimers and of Kv7.2/7.3 heteromultimers were found to be strongly dependent on the [diC8-PIP 2 ] applied to inside-out patches, with differential apparent affinities that correlate with their maximal P o in on-cell mode. Unitary conductance was not affected by PIP 2 . Raising tonic [PIP 2 ] by coexpression of phosphatidylinositol (4)5-kinase increased the maximal P o of both Kv7.2 and Kv7.2/7.3 channels studied in on-cell patches and increased whole-cell Kv7.2, but not Kv7.3, current amplitudes. In cells coexpressed with muscarinic M 1 receptors, bath application of muscarinic agonist reduced the maximal P o of Kv7.2/7.3 channels isolated in on-cell patches. Coexpression of a PIP 2 sequestering construct moderately reduced whole-cell Kv7.2/7.3 currents, and coexpression of a construct containing a PIP 2 phosphatase nearly abolished them. Finally, biochemical analysis of anionic phospholipids in CHO cells stably expressing M 1 receptors shows that PIP 2 and PIP are nearly depleted 1 min after muscarinic stimulation, with an unexpected rebound after 10 min. These results strongly support the direct regulation of Kv7 channels by PIP 2 and its depletion as the mechanism of muscarinic suppression of M channels. Divergent apparent affinities of Kv7.2-7.4 channels for PIP 2 may underlie their highly differential maximal P o observed in cell-attached patches." @default.
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• W2000702625 date "2005-10-26" @default.
• W2000702625 modified "2023-09-30" @default.
• W2000702625 title "Regulation of Kv7 (KCNQ) K⁺Channel Open Probability by Phosphatidylinositol 4,5-Bisphosphate" @default.
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• W2000702625 doi "https://doi.org/10.1523/jneurosci.2597-05.2005" @default.
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