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 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.
McCrossan
Zoe A
ZA
Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
Lewis
Anthony
A
Panaghie
Gianina
G
Jordan
Peter N
PN
Christini
David J
DJ
Lerner
Daniel J
DJ
Abbott
Geoffrey W
GW
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003198:Computer Simulation; D006224:Cricetinae; D051668:Delayed Rectifier Potassium Channels; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051669:Shab Potassium Channels; D051670:Shaw Potassium Channels; D014162:Transfection
D051668:Delayed Rectifier Potassium Channels; C496988:KCNB1 protein, human; C418492:KCNE3 protein, human; C496991:Kcnb1 protein, rat; D046911:Macromolecular Substances; D009479:Neuropeptides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051669:Shab Potassium Channels; D051670:Shaw Potassium Channels; D011188:Potassium