Disease relevance of KCNJ12

• OBJECTIVE: The cardiac inwardly rectifying potassium current IK1 and its molecular correlates Kir2.1 and Kir2.2 play an important role in cardiac repolarisation and in the pathogenesis of hereditary long-QT syndrome (LQTS-7) [1].

High impact information on KCNJ12

• (iii) When Kir2.1 and Kir2.2 channels were coexpressed in Xenopus oocytes the IC(50) for Ba(2+) block of the inward rectifier current differed substantially from the value expected for independent expression of homomeric channels [2].
• The aim of our study was to find out whether heteromerization of Kir2.1 channels with wild-type Kir2.2 and Kir2.3 channels contributes to the phenotype of Andersen's syndrome [2].
• A full-length clone encoding hIRK was isolated from a human atrial cDNA library and functionally expressed in Xenopus oocytes [3].
• 2. Coimmunoprecipitations demonstrated that endogenous Kir2.2 associates with SAP97 in rat cerebellum and heart [4].
• In rat cerebellum, Kir2.2 was present in a punctate pattern along SAP97-positive processes of Bergmann glia in the molecular layer, and colocalized with astrocytes and granule cells in the granule cell layer [4].

Biological context of KCNJ12

• The human inward rectifying K+ channel Kir 2.2 (KCNJ12) gene: gene structure, assignment to chromosome 17p11.1, and identification of a simple tandem repeat polymorphism [5].
• To explore further the relations between hereditary human diseases and K+ channels, we isolated from a human cosmid library the gene encoding the inwardly rectifying K+ channel alpha-subunit Kir 2.2 (KCNJ12) [5].
• We here identified the human Kir2.2 gene in normal individuals, which contained R285 in the deduced amino-acid sequence (hKir2.2/R285) [6].
• Additionally, phosphorylation of the Kir2.2 C terminus by protein kinase A inhibited the association with SAP97 [4].
• 2. Phosphorylation by PKC has been shown to cause an inhibition of Kir2.2 currents, whereas activation of PKA leads to current upregulation [1].

Anatomical context of KCNJ12

• Identification of human Kir2.2 (KCNJ12) gene encoding functional inward rectifier potassium channel in both mammalian cells and Xenopus oocytes [6].
• Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2 [7].
• One of the PCR products we obtained was virtually identical to IRK1 (cloned from a mouse macrophage cell line); the other, which we named hIRK, exhibited < 70% identity to IRK1 [3].
• In rat cardiac ventricular myocytes, Kir2.2 and SAP97 colocalized in striated bands corresponding to T-tubules [4].
• The inwardly rectifying potassium ion channel Kir2.2 has recently been demonstrated to have nuclear and plasma membrane subcellular localization [8].

Associations of KCNJ12 with chemical compounds

• Arginine residue at position 285 (R285) in the intracellular C-terminal domain of inward rectifier potassium channel Kir2.2 is conserved in many species, but missing in previously reported human Kir2.2 sequences [6].
• The effective valency of spermine block (Z0) was highest in Kir2.2 channels while the valencies in Kir2.1 and Kir2.3 channels were not significantly different [9].
• We report the localization of a site that is critical for dofetilide block in hIRK [10].

Other interactions of KCNJ12

• Co-immunoprecipitation reveals that Galpha(q) binds with Kir3.2, but not with Kir2.2 or Kir2 [11].
• Western blot analysis showed clear Kir2.1 and Kir2.2 protein expression, but Kir2.3 protein was undetectable [7].
• AA had no effect on the currents flowing through Kir2.1, Kir2.2, or Kir2.4 channels [12].

Analytical, diagnostic and therapeutic context of KCNJ12

• Detergent-solubilized rat brain and heart extracts were subjected to affinity chromatography using a Kir2.2 C-terminal matrix to purify channel-interacting proteins [13].
• METHODS: Cloned Kir2.2 channels were expressed heterologously in Xenopus oocytes and currents were measured with the double-electrode voltage-clamp technique [1].

References