Related Experiment Video
Updated: Dec 31, 2025
10:20
Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
Published on: November 11, 2016
8.9K
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels as Drug Targets for Neurological Disorders.
1Department of Neuroscience, Columbia University, New York, NY 10027, USA.
Annual Review of Pharmacology and Toxicology
|January 10, 2020
Summary
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate brain activity. Targeting specific HCN isoforms offers potential new therapies for neurological disorders like epilepsy and pain.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are crucial for neuronal excitability.
- Four HCN channel isoforms (HCN1-4) exhibit distinct expression patterns and functions.
- Altered HCN channel expression and function are implicated in various neurological disorders.
Purpose of the Study:
- To review the structure, distribution, and physiological roles of HCN channel isoforms.
- To examine the dysregulation of HCN channels in neurological conditions such as epilepsy, neuropathic pain, and affective disorders.
- To evaluate HCN channels as therapeutic targets and discuss isoform-specific drug design strategies.
Main Methods:
- Literature review of studies on HCN channel structure, function, and expression.
- Analysis of research linking HCN channel alterations to neurological disease pathophysiology.
- Discussion of preclinical and clinical findings related to HCN channel modulation.
Main Results:
- Individual HCN isoforms possess unique properties influencing neuronal activity.
- HCN channel dysfunction is a common feature in epilepsy, neuropathic pain, and affective disorders.
- The auxiliary subunit TRIP8b also plays a role in HCN channel regulation.
Conclusions:
- HCN channels are promising therapeutic targets for neurological conditions.
- Developing drugs that selectively target specific HCN isoforms or TRIP8b could lead to effective treatments.
- Isoform-specific targeting may offer improved efficacy and reduced side effects for neurological therapies.
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.6K
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...
3.6K
01:19Ligand-gated Ion Channels
13.8K
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...
13.8K
01:24Non-gated Ion Channels
7.9K
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....
7.9K
01:26Voltage-gated Ion Channels
10.1K
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...
10.1K
01:26Neurochemical Transmission: Sites of Drug Action
3.4K
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
3.4K
01:21G-Protein Gated Ion Channels
5.5K
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...
5.5K