QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 26, 2005, 25(43):9825-9835; doi:10.1523/JNEUROSCI.2597-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Li, Y. Articles by Shapiro, M. S. Search for Related Content PubMed PubMed Citation Articles by Li, Y. Articles by Shapiro, M. S.

 Previous Article  |  Next Article 

Cellular/Molecular
Regulation of Kv7 (KCNQ) K⁺ Channel Open Probability by Phosphatidylinositol 4,5-Bisphosphate

Yang Li,¹ Nikita Gamper,¹ Donald W. Hilgemann,² and Mark S. Shapiro¹

¹Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, and ²Department of Physiology, University of Texas Southwest Medical Center, Dallas, Texas 75235-9040

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 (PIP₂) and PIP₂ depletion to underlie muscarinic receptor inhibition. We studied regulation of Kv7.2-7.4 channels by PIP₂ 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-PIP₂] 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 PIP₂. Raising tonic [PIP₂] 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 M₁ 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 PIP₂ sequestering construct moderately reduced whole-cell Kv7.2/7.3 currents, and coexpression of a construct containing a PIP₂ phosphatase nearly abolished them. Finally, biochemical analysis of anionic phospholipids in CHO cells stably expressing M₁ receptors shows that PIP₂ 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 PIP₂ and its depletion as the mechanism of muscarinic suppression of M channels. Divergent apparent affinities of Kv7.2-7.4 channels for PIP₂ may underlie their highly differential maximal P_o observed in cell-attached patches.

Key words: lipid signaling; potassium channel; M current; phosphatidylinositol 4,5-bisphosphate; single channel; gating; patch clamp

---

Received June 23, 2005; revised August 26, 2005; accepted September 9, 2005.

This article has been cited by other articles:

				A. Yaradanakul, T.-M. Wang, V. Lariccia, M.-J. Lin, C. Shen, X. Liu, and D. W. Hilgemann Massive Ca-induced Membrane Fusion and Phospholipid Changes Triggered by Reverse Na/Ca Exchange in BHK Fibroblasts J. Gen. Physiol., June 30, 2008; 132(1): 29 - 50. [Abstract] [Full Text] [PDF]

				Z. Jia, J. Bei, L. Rodat-Despoix, B. Liu, Q. Jia, P. Delmas, and H. Zhang NGF Inhibits M/KCNQ Currents and Selectively Alters Neuronal Excitability in Subsets of Sympathetic Neurons Depending on their M/KCNQ Current Background J. Gen. Physiol., May 26, 2008; 131(6): 575 - 587. [Abstract] [Full Text] [PDF]

				D. Peroz, N. Rodriguez, F. Choveau, I. Baro, J. Merot, and G. Loussouarn Kv7.1 (KCNQ1) properties and channelopathies J. Physiol., April 1, 2008; 586(7): 1785 - 1789. [Abstract] [Full Text] [PDF]

				Y. Haitin and B. Attali The C-terminus of Kv7 channels: a multifunctional module J. Physiol., April 1, 2008; 586(7): 1803 - 1810. [Abstract] [Full Text] [PDF]

				C. C. Hernandez, O. Zaika, G. P. Tolstykh, and M. S. Shapiro Regulation of neural KCNQ channels: signalling pathways, structural motifs and functional implications J. Physiol., April 1, 2008; 586(7): 1811 - 1821. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, Q. Tong, J. Medina, A. Vandewalle, A. Staruschenko, V. Bugaj, and J. D. Stockand Molecular Determinants of PI(4,5)P2 and PI(3,4,5)P3 Regulation of the Epithelial Na+ Channel J. Gen. Physiol., September 24, 2007; 130(4): 399 - 413. [Abstract] [Full Text] [PDF]

				D. A. Brown, S. A. Hughes, S. J. Marsh, and A. Tinker Regulation of M(Kv7.2/7.3) channels in neurons by PIP2 and products of PIP2 hydrolysis: significance for receptor-mediated inhibition J. Physiol., August 1, 2007; 582(3): 917 - 925. [Abstract] [Full Text] [PDF]

				B.-C. Suh and B. Hille Regulation of KCNQ channels by manipulation of phosphoinositides J. Physiol., August 1, 2007; 582(3): 911 - 916. [Abstract] [Full Text] [PDF]

				N. Gamper and M. S. Shapiro Target-specific PIP2 signalling: how might it work? J. Physiol., August 1, 2007; 582(3): 967 - 975. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, Q. Tong, A. Staruschenko, and J. D. Stockand Binding and direct activation of the epithelial Na+ channel (ENaC) by phosphatidylinositides J. Physiol., April 15, 2007; 580(2): 365 - 372. [Abstract] [Full Text] [PDF]

				B.-C. Suh, T. Inoue, T. Meyer, and B. Hille Rapid Chemically Induced Changes of PtdIns(4,5)P2 Gate KCNQ Ion Channels Science, December 1, 2006; 314(5804): 1454 - 1457. [Abstract] [Full Text] [PDF]

				D. Kang, J. Han, and D. Kim Mechanism of inhibition of TREK-2 (K2P10.1) by the Gq-coupled M3 muscarinic receptor Am J Physiol Cell Physiol, October 1, 2006; 291(4): C649 - C656. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, J. Medina, N. Gamper, H. Genth, J. D. Stockand, and A. Staruschenko Rapid Translocation and Insertion of the Epithelial Na+ Channel in Response to RhoA Signaling J. Biol. Chem., September 8, 2006; 281(36): 26520 - 26527. [Abstract] [Full Text] [PDF]

				O. Zaika, L. S. Lara, N. Gamper, D. W. Hilgemann, D. B. Jaffe, and M. S. Shapiro Angiotensin II regulates neuronal excitability via phosphatidylinositol 4,5-bisphosphate-dependent modulation of Kv7 (M-type) K+ channels J. Physiol., August 15, 2006; 575(1): 49 - 67. [Abstract] [Full Text] [PDF]

				J. Robbins, S. J. Marsh, and D. A. Brown Probing the regulation of M (Kv7) potassium channels in intact neurons with membrane-targeted peptides. J. Neurosci., July 26, 2006; 26(30): 7950 - 7961. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, Q. Tong, A. Staruschenko, H.-P. Ma, and J. D. Stockand Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides Am J Physiol Renal Physiol, May 1, 2006; 290(5): F949 - F957. [Abstract] [Full Text] [PDF]

				X. Chen, E. M. Talley, N. Patel, A. Gomis, W. E. McIntire, B. Dong, F. Viana, J. C. Garrison, and D. A. Bayliss Inhibition of a background potassium channel by Gq protein {alpha}-subunits PNAS, February 28, 2006; 103(9): 3422 - 3427. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help