Introduction of KCNJ4
KCNJ4 (also known as Kir2.3, IRK3, HIRK2, HRK1), is encoded by the KCNJ4 gene. It belongs to inwardly rectifying K+ (Kir) channels family, Kir2 subfamily, which are characterized by strong inward rectification and constitutive activity and are detected in various cells, including neurons, glial cells, cardiac and skeletal myocytes, epithelial cells, and macrophages. As one of four identified Kir2 subfamily members in mammals, KCNJ4 can also tetramerize to form functional inwardly rectifying channels, in which each monomer contains two transmembrane helix domains (M1 and M2), an ion-selective P-loop between M1 and M2, and cytoplasmic N- and C-terminal domains. The distribution of KCNJ4 is predominantly focused in both heart and brain, especially in the cardiac myocytes and forebrain region. Furthermore, it is documented that KCNJ4 is mainly localized at the postsynaptic membrane of excitatory synapses.
|Basic Information of KCNJ4|
|Protein Name||Inward rectifier potassium channel 4|
|Aliases||Kir2.3, IRK3, HIRK2, HRK1|
|Organism||Homo sapiens (Human)|
Function of KCNJ4 Membrane Protein
As one the member of Kir family, KCNJ4 may play important roles in the regulation of resting membrane potential, cellular excitability and potassium homeostasis in the nervous system and various peripheral tissues. KCNJ4 is reported to participate in the cardiac classical inward rectifier potassium currents (IK1) in neonatal rat cardiomyocytes, responsible for stabilizing the resting membrane potential, determining excitation threshold, and initiating the final repolarization phase of the cardiac action potential. As one cationic amphiphilic drug, carvedilol can inhibit KCNJ4 channels by interfering with the phosphatidylinositol-4,5-bisphosphate (PIP2)-channel interaction, a critical factor for the activation of Kir channels. In the nervous system, neuronal KCNJ4 distributes diffusely in the nuclei and on the plasma membrane of pyramidal cells in the CA3 region of hippocampus, which is related to cognition, memory, emotion and neuropsychiatric disorders. Notably, various intra- and extra-cellular signal molecules including ATP, protons, and protein kinase C can modulate KCNJ4 channels activity. KCNJ4 channels can directly couple to G proteins, which allows these channels to contribute to neurotransmission and cell-cell communications.
Fig.1 Model of Kir2.3 channel regulation by TIP-1. (Yan, 2009)
Application of KCNJ4 Membrane Protein in Literature
In this article, the authors examined the cross-talk between cholesterol and PIP2 in the regulation of Kir2 channels and they found that dialysis of neomycin will lead to a decrease in Kir2.1 and Kir2.3 current amplitudes (current rundown), consistent with a reduction in PIP2 levels. While the reduction would be significantly delayed by cholesterol depletion, suggesting that cholesterol depletion strengthened the interaction between Kir2 channels and PIP2.
This article identified that the precise localization in the forebrain of Kir2.3 was focused on the postsynaptic membrane of excitatory synapses, where it played important role in the formation of the resting membrane potential of the spines and then would affect the response of N-methyl-D-aspartic acid receptor channels at the excitatory postsynaptic membrane.
The authors demonstrated that the epidermal growth factor receptor (EGFR) tyrosine kinase can up-regulate the KIR2.3 channel via phosphorylation of the Y234 residue, which might be involved in the endogenous regulation of cellular electrical activity.
This article used the Xenopus oocyte expression assay to test the effects of various neurosteroids on Kir2.3 channels, and revealed that pregnenolone sulfate (PREGS) was a positive modulator of Kir2.3 channels, which can regulate the activation of Kir2.3-containing Kir2 heteromeric channels.
This article firstly identified that Kir2.3 channels were completely suppressed by co-expression with G-protein beta/gamma subunits, consistent with suppression of Kir2.3 currents resulting from a direct protein-protein interaction between the channel and G-protein beta/gamma subunits.
KCNJ4 Preparation Options
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