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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 3, 2003, 23(22):8077-8091

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 (29) Citing Articles via Google Scholar Google Scholar Articles by McCrossan, Z. A. Articles by Abbott, G. W. Search for Related Content PubMed PubMed Citation Articles by McCrossan, Z. A. Articles by Abbott, G. W.

 Previous Article  |  Next Article 

MinK-Related Peptide 2 Modulates Kv2.1 and Kv3.1 Potassium Channels in Mammalian Brain

Zoe A. McCrossan,¹ Anthony Lewis,¹ Gianina Panaghie,^1,3 Peter N. Jordan,^1,4 David J. Christini,¹ Daniel J. Lerner,^1,2 and Geoffrey W. Abbott^1,2

¹Division of Cardiology, Department of Medicine, ²Department of Pharmacology, ³Graduate Program in Pharmacology, and ⁴Graduate Program in Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021

Delayed rectifier potassium current diversity and regulation are essential for signal processing and integration in neuronal circuits. Here, we investigated a neuronal role for MinK-related peptides (MiRPs), membrane-spanning modulatory subunits that generate phenotypic diversity in cardiac potassium channels. Native coimmunoprecipitation from rat brain membranes identified two novel potassium channel complexes, MiRP2-Kv2.1 and MiRP2-Kv3.1b. MiRP2 reduces the current density of both channels, slows Kv3.1b activation, and slows both activation and deactivation of Kv2.1. Altering native MiRP2 expression levels by RNAi gene silencing or cDNA transfection toggles the magnitude and kinetics of endogenous delayed rectifier currents in PC12 cells and hippocampal neurons. Computer simulations predict that the slower gating of Kv3.1b in complexes with MiRP2 will broaden action potentials and lower sustainable firing frequency. Thus, MiRP2, unlike other known neuronal subunits, provides a mechanism for influence over multiple delayed rectifier potassium currents in mammalian CNS via modulation of subunits from structurally and kinetically distinct subfamilies.

Key words: delayed rectifier; hippocampus; KCNE3; Kv2.1; Kv3.1; potassium channel; RNAi

---

Received June 9, 2003; revised July 5, 2003; accepted July 10, 2003.

This article has been cited by other articles:

				D. I. Levy, S. Wanderling, D. Biemesderfer, and S. A. N. Goldstein MiRP3 acts as an accessory subunit with the BK potassium channel Am J Physiol Renal Physiol, August 1, 2008; 295(2): F380 - F387. [Abstract] [Full Text] [PDF]

				G. C. L. Bett and R. L. Rasmusson Modification of K+ channel-drug interactions by ancillary subunits J. Physiol., February 15, 2008; 586(4): 929 - 950. [Abstract] [Full Text] [PDF]

				Y. Wang and F. Sesti Molecular Mechanisms Underlying KVS-1-MPS-1 Complex Assembly Biophys. J., November 1, 2007; 93(9): 3083 - 3091. [Abstract] [Full Text] [PDF]

				E. Choi and G. W. Abbott The MiRP2-Kv3.4 Potassium Channel: Muscling In on Alzheimer's Disease Mol. Pharmacol., September 1, 2007; 72(3): 499 - 501. [Abstract] [Full Text] [PDF]

				A. H. Gittis and S. du Lac Firing Properties of GABAergic Versus Non-GABAergic Vestibular Nucleus Neurons Conferred by a Differential Balance of Potassium Currents J Neurophysiol, June 1, 2007; 97(6): 3986 - 3996. [Abstract] [Full Text] [PDF]

				T. K. Roepke, A. Anantharam, P. Kirchhoff, S. M. Busque, J. B. Young, J. P. Geibel, D. J. Lerner, and G. W. Abbott The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion J. Biol. Chem., August 18, 2006; 281(33): 23740 - 23747. [Abstract] [Full Text] [PDF]

				Y. Li, S. Y. Um, and T. V. Mcdonald Voltage-Gated Potassium Channels: Regulation by Accessory Subunits Neuroscientist, June 1, 2006; 12(3): 199 - 210. [Abstract] [PDF]

				E. Gordon, T. K. Roepke, and G. W. Abbott Endogenous KCNE Subunits Govern Kv2.1 K+ Channel Activation Kinetics in Xenopus Oocyte Studies Biophys. J., February 15, 2006; 90(4): 1223 - 1231. [Abstract] [Full Text] [PDF]

				G. W. Abbott, M. H. Butler, and S. A. N. Goldstein Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis FASEB J, February 1, 2006; 20(2): 293 - 301. [Abstract] [Full Text] [PDF]

				S. Bendahhou, C. Marionneau, K. Haurogne, M.-M. Larroque, R. Derand, V. Szuts, D. Escande, S. Demolombe, and J. Barhanin In vitro molecular interactions and distribution of KCNE family with KCNQ1 in the human heart Cardiovasc Res, August 15, 2005; 67(3): 529 - 538. [Abstract] [Full Text] [PDF]

				M. L Dallas, L. Atkinson, C. J Milligan, N. P Morris, D. I Lewis, S. A Deuchars, and J. Deuchars Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii J. Physiol., February 1, 2005; 562(3): 655 - 672. [Abstract] [Full Text] [PDF]

				S. D. Gage and W. R. Kobertz KCNE3 Truncation Mutants Reveal a Bipartite Modulation of KCNQ1 K+ Channels J. Gen. Physiol., November 29, 2004; 124(6): 759 - 771. [Abstract] [Full Text] [PDF]

				A. Lewis, Z. A. McCrossan, and G. W. Abbott MinK, MiRP1, and MiRP2 Diversify Kv3.1 and Kv3.2 Potassium Channel Gating J. Biol. Chem., February 27, 2004; 279(9): 7884 - 7892. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help