MiRP3 acts as an accessory subunit with the BK potassium channel.
MinK-related peptides (MiRPs) are single-span membrane proteins that assemble with specific voltage-gated K+ (Kv) channel alpha-subunits to establish gating kinetics, unitary conductance, expression level, and pharmacology of the mixed complex. MiRP3 (encoded by the KCNE4 gene) has been shown to alter the behavior of some Kv alpha-subunits in vitro but its natural partners and physiologic functions are unknown. Seeking in vivo partners for MiRP3, immunohistochemistry was used to localize its expression to a unique subcellular site, the apical membrane of renal intercalated cells, where one potassium channel type has been recorded, the calcium- and voltage-gated channel BK. Overlapping staining of these two proteins was found in rabbit intercalated cells, and MiRP3 and BK subunits expressed in tissue culture cells were found to form detergent-stable complexes. Electrophysiologic and biochemical evaluation showed MiRP3 to act on BK to reduce current density in two fashions: shifting the current-voltage relationship to more depolarized voltages in a calcium-dependent fashion ( approximately 10 mV at normal intracellular calcium levels) and accelerating degradation of MiRP3-BK complexes. The findings suggest a role for MiRP3 modulation of BK-dependent urinary potassium excretion.
Levy
Daniel I
DI
Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, Illinois, USA. dlevy@medicine.bsd.uchicago.edu
Wanderling
Sherry
S
Biemesderfer
Daniel
D
Goldstein
Steve A N
SA
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000652:urine; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D014162:Transfection
C498897:KCNE4 protein, human; C531570:KCNE4 protein, rat; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D011188:Potassium