RGD Reference Report - Regulation of the Kv2.1 potassium channel by MinK and MiRP1. - Rat Genome Database

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Regulation of the Kv2.1 potassium channel by MinK and MiRP1.

Authors: McCrossan, ZA  Roepke, TK  Lewis, A  Panaghie, G  Abbott, GW 
Citation: McCrossan ZA, etal., J Membr Biol. 2009 Mar;228(1):1-14. doi: 10.1007/s00232-009-9154-8. Epub 2009 Feb 14.
RGD ID: 7243947
Pubmed: PMID:19219384   (View Abstract at PubMed)
PMCID: PMC2849987   (View Article at PubMed Central)
DOI: DOI:10.1007/s00232-009-9154-8   (Journal Full-text)

Kv2.1 is a voltage-gated potassium (Kv) channel alpha-subunit expressed in mammalian heart and brain. MinK-related peptides (MiRPs), encoded by KCNE genes, are single-transmembrane domain ancillary subunits that form complexes with Kv channel alpha-subunits to modify their function. Mutations in human MinK (KCNE1) and MiRP1 (KCNE2) are associated with inherited and acquired forms of long QT syndrome (LQTS). Here, coimmunoprecipitations from rat heart tissue suggested that both MinK and MiRP1 form native cardiac complexes with Kv2.1. In whole-cell voltage-clamp studies of subunits expressed in CHO cells, rat MinK and MiRP1 reduced Kv2.1 current density three- and twofold, respectively; slowed Kv2.1 activation (at +60 mV) two- and threefold, respectively; and slowed Kv2.1 deactivation less than twofold. Human MinK slowed Kv2.1 activation 25%, while human MiRP1 slowed Kv2.1 activation and deactivation twofold. Inherited mutations in human MinK and MiRP1, previously associated with LQTS, were also evaluated. D76N-MinK and S74L-MinK reduced Kv2.1 current density (threefold and 40%, respectively) and slowed deactivation (60% and 80%, respectively). Compared to wild-type human MiRP1-Kv2.1 complexes, channels formed with M54T- or I57T-MiRP1 showed greatly slowed activation (tenfold and fivefold, respectively). The data broaden the potential roles of MinK and MiRP1 in cardiac physiology and support the possibility that inherited mutations in either subunit could contribute to cardiac arrhythmia by multiple mechanisms.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcnb1Ratplasma membrane located_inIDA PMID:19219384UniProt 
Kcne1Ratplasma membrane located_inIDA PMID:19219384UniProt 
Kcne2Ratplasma membrane located_inIDA PMID:19219384UniProt 
Kcnb1Ratvoltage-gated potassium channel complex part_ofIDA PMID:19219384UniProt 
Kcne1Ratvoltage-gated potassium channel complex located_inIDA PMID:19219384UniProt 
Kcne2Ratvoltage-gated potassium channel complex located_inIDA PMID:19219384UniProt 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Kcnb1  (potassium voltage-gated channel subfamily B member 1)
Kcne1  (potassium voltage-gated channel subfamily E regulatory subunit 1)
Kcne2  (potassium voltage-gated channel subfamily E regulatory subunit 2)


Additional Information