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

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 potassiu...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-09, Vol.23 (22), p.8077-8091
Main Authors: McCrossan, Zoe A, Lewis, Anthony, Panaghie, Gianina, Jordan, Peter N, Christini, David J, Lerner, Daniel J, Abbott, Geoffrey W
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Brain - cytology
Brain - metabolism
Cell Membrane - metabolism
Cells, Cultured
Cellular/Molecular
CHO Cells
Computer Simulation
Cricetinae
Delayed Rectifier Potassium Channels
Hippocampus - cytology
Hippocampus - metabolism
Humans
Macromolecular Substances
Mammalia
Neurons - metabolism
Neuropeptides - genetics
Neuropeptides - metabolism
Patch-Clamp Techniques
PC12 Cells
Potassium - metabolism
Potassium Channels - genetics
Potassium Channels - metabolism
Potassium Channels, Voltage-Gated
Protein Subunits - genetics
Protein Subunits - metabolism
Rats
Rats, Sprague-Dawley
Shab Potassium Channels
Shaw Potassium Channels
Transfection
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.23-22-08077.2003