Related Experiment Video
Updated: Jun 3, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Inverse agonist-like action of cadmium on G-protein-gated inward-rectifier K(+) channels
Atsushi Inanobe1, Takanori Matsuura, Atsushi Nakagawa
1Department of Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan. inanobe@pharma2.med.osaka-u.ac.jp
Abstract:
The gate at the pore-forming domain of potassium channels is allosterically controlled by a stimulus-sensing domain. Using Cd²(+) as a probe, we examined the structural elements responsible for gating in an inward-rectifier K(+) channel (Kir3.2). One of four endogenous cysteines facing the cytoplasm contributes to a high-affinity site for inhibition by internal Cd²(+). Crystal structure of its cytoplasmic domain in complex with Cd²(+) reveals that octahedral coordination geometry supports the high-affinity binding. This mode of action causes the tethering of the N-terminus to CD loop in the stimulus-sensing domain, suggesting that their conformational changes participate in gating and Cd²(+) inhibits Kir3.2 by trapping the conformation in the closed state like "inverse agonist".
Related Concept Videos
G-Protein Gated Ion Channels
Sensory organs,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
GPCRs Regulate Adenylyl Cylase Activity
Two...
GPCR Desensitization
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Activation and Inactivation of G Proteins

