MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating.
High frequency firing in mammalian neurons requires ultra-rapid delayed rectifier potassium currents generated by homomeric or heteromeric assemblies of Kv3.1 and Kv3.2 potassium channel alpha subunits. Kv3.1 alpha subunits can also form slower activating channels by coassembling with MinK-related peptide 2 (MiRP2), a single transmembrane domain potassium channel ancillary subunit. Here, using channel subunits cloned from rat and expressed in Chinese hamster ovary cells, we show that modulation by MinK, MiRP1, and MiRP2 is a general mechanism for slowing of Kv3.1 and Kv3.2 channel activation and deactivation and acceleration of inactivation, creating a functionally diverse range of channel complexes. MiRP1 also negatively shifts the voltage dependence of Kv3.1 and Kv3.2 channel activation. Furthermore, MinK, MiRP1, and MiRP2 each form channels with Kv3.1-Kv3.2 heteromers that are kinetically distinct from one another and from MiRP/homomeric Kv3 channels. The findings illustrate a mechanism for dynamic expansion of the functional repertoire of Kv3.1 and Kv3.2 potassium currents and suggest roles for these alpha subunits outside the scope of sustained rapid neuronal firing.
Lewis
Anthony
A
Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
McCrossan
Zoe A
ZA
Abbott
Geoffrey W
GW
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004553:Electric Conductivity; D004594:Electrophysiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels; D051670:Shaw Potassium Channels; D013329:Structure-Activity Relationship; D014162:Transfection
C116766:KCNAB3 protein, human; C418492:KCNE3 protein, human; C098254:Kcnc1 protein, rat; C484268:Kcne1 protein, rat; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels; D051670:Shaw Potassium Channels; C059983:potassium channel protein I(sk)