RGD Reference Report - Heterogeneity of ATP-sensitive K+ channels in cardiac myocytes: enrichment at the intercalated disk. - Rat Genome Database

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Heterogeneity of ATP-sensitive K+ channels in cardiac myocytes: enrichment at the intercalated disk.

Authors: Hong, M  Bao, L  Kefaloyianni, E  Agullo-Pascual, E  Chkourko, H  Foster, M  Taskin, E  Zhandre, M  Reid, DA  Rothenberg, E  Delmar, M  Coetzee, WA 
Citation: Hong M, etal., J Biol Chem. 2012 Nov 30;287(49):41258-67. doi: 10.1074/jbc.M112.412122. Epub 2012 Oct 12.
RGD ID: 7296922
Pubmed: PMID:23066018   (View Abstract at PubMed)
PMCID: PMC3510824   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M112.412122   (Journal Full-text)

Ventricular ATP-sensitive potassium (K(ATP)) channels link intracellular energy metabolism to membrane excitability and contractility. Our recent proteomics experiments identified plakoglobin and plakophilin-2 (PKP2) as putative K(ATP) channel-associated proteins. We investigated whether the association of K(ATP) channel subunits with junctional proteins translates to heterogeneous subcellular distribution within a cardiac myocyte. Co-immunoprecipitation experiments confirmed physical interaction between K(ATP) channels and PKP2 and plakoglobin in rat heart. Immunolocalization experiments demonstrated that K(ATP) channel subunits (Kir6.2 and SUR2A) are expressed at a higher density at the intercalated disk in mouse and rat hearts, where they co-localized with PKP2 and plakoglobin. Super-resolution microscopy demonstrate that K(ATP) channels are clustered within nanometer distances from junctional proteins. The local K(ATP) channel density, recorded in excised inside-out patches, was larger at the cell end when compared with local currents recorded from the cell center. The K(ATP) channel unitary conductance, block by MgATP and activation by MgADP, did not differ between these two locations. Whole cell K(ATP) channel current density (activated by metabolic inhibition) was approximately 40% smaller in myocytes from mice haploinsufficient for PKP2. Experiments with excised patches demonstrated that the regional heterogeneity of K(ATP) channels was absent in the PKP2 deficient mice, but the K(ATP) channel unitary conductance and nucleotide sensitivities remained unaltered. Our data demonstrate heterogeneity of K(ATP) channel distribution within a cardiac myocyte. The higher K(ATP) channel density at the intercalated disk implies a possible role at the intercellular junctions during cardiac ischemia.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
intercalated disc  IDA 7296922 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIKcnj11 (Rattus norvegicus)7296922; 7296922 RGD 
protein binding  IPIPkp2 (Rattus norvegicus) and Jup (Rattus norvegicus)7296922 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Jup  (junction plakoglobin)
Kcnj11  (potassium inwardly-rectifying channel, subfamily J, member 11)
Pkp2  (plakophilin 2)


Additional Information