Related Experiment Video
Updated: Aug 5, 2025
08:33
Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
2.0K
Subunit gating resulting from individual protonation events in Kir2 channels
Grigory Maksaev1, Michael Bründl-Jirout2, Anna Stary-Weinzinger2
1Department of Cell Biology and Physiology and the Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
Research Square
|March 30, 2023
Summary
Inwardly rectifying potassium (Kir) channels control cell potential. Mutations reveal pH-dependent subconductance states, showing how protonation affects ion flow and channel gating.
Area of Science:
- Molecular biology
- Biophysics
- Ion channel physiology
Background:
- Inwardly rectifying potassium (Kir) channels stabilize membrane potential, crucial for physiological functions.
- Channel activity is regulated by cytoplasmic modulators at the helix bundle crossing (HBC).
Approach:
- Introduced a negative charge (G178D) in Kir2.2 channels to force opening.
- Utilized single-channel recordings and molecular dynamics simulations to analyze channel behavior.
- Investigated pH-dependent gating and conductance in mutant Kir2.2 channels.
Key Points:
- Mutant Kir2.2 channels exhibit pH-dependent subconductance levels, reflecting individual subunit events.
- Decreasing cytoplasmic pH shifts probability towards lower conductance states.
- Protonation of pore-lining residues alters pore solvation, ion occupancy, and K+ conductance.
Conclusions:
- Individual protonation events create distinct, uncoordinated conductance states.
- Subconductance gating is intimately linked to ion channel gating and conductance.
- This study resolves and explains subconductance gating mechanisms in Kir channels.
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K
01:24Non-gated Ion Channels
6.9K
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
6.9K
01:21G-Protein Gated Ion Channels
4.7K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
4.7K
01:19Ligand-gated Ion Channels
12.5K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
12.5K
01:22Activation and Inactivation of G Proteins
7.3K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
7.3K
01:12Mechanically-gated Ion Channels
6.5K
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
6.5K