Related Experiment Video
Updated: Aug 30, 2025
10:14
Recapitulation of an Ion Channel IV Curve Using Frequency Components
Published on: February 8, 2011
13.6K
Effective Perturbations by Small-Molecule Modulators on Voltage-Dependent Hysteresis of Transmembrane Ionic Currents
Sheng-Nan Wu1,2,3, Chao-Liang Wu4, Hsin-Yen Cho1
1Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
International Journal of Molecular Sciences
|August 26, 2022
Summary
Small molecules modulate voltage-dependent hysteresis (Hys(V)) in ion channels, affecting cell excitability. This study investigates how various compounds alter Hys(V) in different currents, revealing potential impacts on cellular electrical activity.
Area of Science:
- Electrophysiology
- Pharmacology
- Cellular Neuroscience
Background:
- Non-linear voltage-dependent hysteresis (Hys(V)) in voltage-gated ion currents is crucial for regulating membrane excitability.
- Triangular voltage ramps (Vramp) are effective in activating and studying Hys(V) in excitable cells.
- Small molecules can significantly influence the strength of Hys(V) across various ionic currents.
Purpose of the Study:
- To investigate the effects of diverse small molecules on the voltage-dependent hysteresis (Hys(V)) of different voltage-gated ion currents.
- To characterize how perturbations in Hys(V) by these modulators impact the electrical behavior of excitable cells.
Main Methods:
- Activation of ionic currents using isosceles-triangular ramp voltage (Vramp) via digital-to-analog conversion.
- Application of various small molecules, including pirfenidone, dexmedetomidine, oxaliplatin, honokiol, lutein, UCL-2077, SM-102, isoplumbagin, plumbagin, remdesivir, QO-58, zingerone, tefluthrin, t-butyl hydroperoxide, dapagliflozin, esaxerenone, and mirogabalin.
- Quantification of the changes in Hys(V) strength and magnitude for different ion currents (Ih, erg-K+, M-type K+, L-type Ca2+, INa(P)).
Main Results:
- Pirfenidone, dexmedetomidine, honokiol, and lutein decreased Ih Hys(V) strength, while oxaliplatin enhanced it.
- UCL-2077, SM-102, isoplumbagin, and plumbagin diminished erg-K+ current Hys(V); remdesivir decreased and QO-58 increased M-type K+ current Hys(V).
- Zingerone attenuated L-type Ca2+ current Hys(V); tefluthrin and t-butyl hydroperoxide enhanced INa(P) Hys(V), with dapagliflozin reversing these effects. Esaxerenone, mirogabalin, and dapagliflozin inhibited INa(P) strength.
Conclusions:
- Small molecules exhibit diverse effects on the Hys(V) of various voltage-gated ion currents.
- These modulations of Hys(V) strength are likely to influence the overall electrical activity and functional properties of excitable cells.
- The study provides a comprehensive overview of small-molecule interactions with ion channel hysteresis, offering insights into potential therapeutic targets.
Keywords:
L-type Ca2+ currentM-type K+ currenterg-mediated K+ currenthyperpolarization-activated cation currentpersistent Na+ currentsmall-molecule modulatorsvoltage-dependent hysteresisMore Related Videos
08:07Assembly and Characterization of Biomolecular Memristors Consisting of Ion Channel-doped Lipid Membranes
Published on: March 9, 2019
7.9K
13:56Modeling Biological Membranes with Circuit Boards and Measuring Electrical Signals in Axons: Student Laboratory Exercises
Published on: January 18, 2011
22.8K
Related Concept Videos
01:12Mechanically-gated Ion Channels
6.6K
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...
6.6K
01:26Voltage-gated Ion Channels
8.5K
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
8.5K
01:24Non-gated Ion Channels
7.0K
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....
7.0K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.5K
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...
2.5K
01:24Resting Membrane Potential
19.1K
The relative difference in electrical charge, or voltage, between the inside and the outside of a cell membrane, is called the membrane potential. It is generated by differences in permeability of the membrane to various ions and the concentrations of these ions across the membrane.
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
19.1K
01:21The Resting Membrane Potential
134.5K
Overview
134.5K