Inwardly Rectifying Potassium Channel Assays
Inwardly rectifying potassium channels (IRK) are a type of lipid-gated potassium channel. They are activated by phosphatidylinositol 4,5-bisphosphate (PIP2). IRK channels have a pore domain that is similar to that of voltage-gated ion channels and flanking transmembrane segments (TMSs). They can exist as homo- or heterooligomers in the membrane, with each monomer containing between 2 and 4 TMSs. These proteins transport potassium, with a larger proclivity for K+ uptake than for K+ export.
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Structure
The P domains of IRK channels share just a small amount of sequence similarity with the VIC family. Inward rectifiers help set cellular membrane potentials, and depolarization causes these channels to close, allowing for long-duration action potentials with a plateau phase.
Feature
Inwardly rectifying potassium channel is one that passes current more easily in the inward direction than in the outward direction. It is thought to play a key function in controlling neuronal activity by assisting in the stabilization of the cell's resting membrane potential. In voltage clamp, inward current is represented by a downward deflection, whereas outward current is represented by an upward deflection. Inwardly rectifying K+ channels facilitate the flow of positively charged K+ ions into the cell at membrane potentials negative to potassium's reversal potential, bringing the membrane potential back to the resting potential.
Published Data
| Paper Title | Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel |
| Journal | Nature Communications |
| Published | 2019 |
| Abstract | Inwardly rectifying potassium channel (GIRK) control of neurotransmission is important. The G protein βγ subunit (Gβγ), which is released from the heterotrimeric G protein (Gαβγ) upon activation of G protein-coupled receptors, directly binds to GIRK and causes it to open (GPCRs). By integrating cell-based BRET experiments with NMR investigations in a recreated membrane environment, they look into the structural mechanism underlying the Gi/o family-specific activation of GIRK. |
| Result |
The schematic and example findings from the BRET tests utilizing NLuc-tagged GRK and GIRK are shown in Fig. a–d. Fluorescence imaging verified the presence of G proteins and GIRK on the plasma membrane. The addition of Met-enkephalin promoted the activation of DOR and the subsequent association between Venus-G and GRK-Luc, resulting in energy transfer between them to raise the BRET signal in HEK293T cells that express Venus-tagged G and GRK-Luc, together with G and the delta opioid receptor (DOR).
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Fig.1. Measuring Gα specificity in Gβγ-GIRK binding. (Kano, 2019)
Reference
- Kano, H.; et al. Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel. Nature communications. 2019, 10(1): 1-13.
