MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain.

Full Abstract

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 beta subunits, provides a mechanism for influence over multiple delayed rectifier potassium currents in mammalian CNS via modulation of alpha subunits from structurally and kinetically distinct subfamilies.

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Author information

Author/s: McCrossan, Zoe A (ZA); Lewis, Anthony (A); Panaghie, Gianina (G); Jordan, Peter N (PN); Christini, David J (DJ); Lerner, Daniel J (DJ); Abbott, Geoffrey W (GW);

Affiliation: Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2003-Sep; vol 23 (issue 22) : pp 8077-91

Dates: Created 2003/09/04; Completed 2003/10/02; Revised 2006/11/15;

PMID: 12954870, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Action Potentials - physiology
Animals
Brain - cytology; metabolism
CHO Cells
Cell Membrane - metabolism
Cells, Cultured
Computer Simulation
Cricetinae
Delayed Rectifier Potassium Channels
Hippocampus - cytology; metabolism
Humans
Macromolecular Substances
Neurons - metabolism

Neurons - metabolism
Neuropeptides - genetics; metabolism
PC12 Cells
Patch-Clamp Techniques
Potassium - metabolism
Potassium Channels - genetics; metabolism
Potassium Channels, Voltage-Gated
Protein Subunits - genetics; metabolism
Rats
Rats, Sprague-Dawley
Shab Potassium Channels
Shaw Potassium Channels
Transfection

Associated Chemicals: Delayed Rectifier Potassium Channels (0) ; KCNB1 protein, human (0) ; KCNE3 protein, human (0) ; Kcnb1 protein, rat (0) ; Macromolecular Substances (0) ; Neuropeptides (0) ; Potassium Channels (0) ; Potassium Channels, Voltage-Gated (0) ; Protein Subunits (0) ; Shab Potassium Channels (0) ; Shaw Potassium Channels (0) ; Potassium (7440-09-7)

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