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Related Concept Videos

Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

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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...
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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

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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...
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Ligand-gated Ion Channels01:19

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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...
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The Role of Ion Channels in Neuronal Computation01:19

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A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
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Mechanically-gated Ion Channels01:12

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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...
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Non-gated Ion Channels01:24

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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.
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Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry
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[Calcium-activated chloride channels: structure, properties, role in physiological and pathological processes].

V V Grigoriev1

  • 1Institute of Physiologically Active Compounds of the Russian Academy of Sciences, Moscow, Russia.

Biomeditsinskaia Khimiia
|March 1, 2021
PubMed
Summary

Calcium-activated chloride channels (CaCC), formed by anoctamine 1 (ANO1/TMEM16A), are crucial for physiological functions and implicated in diseases like cancer and hypertension. This review explores compounds that modulate CaCC activity for therapeutic potential.

Keywords:
Ca2+-activated chloride channels (CaCC)CaCC blockers/modulatorsCaCC molecular structurecell signaling pathwaysrole of CaCC in pathophysiological processesrole of CaCC in physiological processes

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Area of Science:

  • Physiology
  • Molecular Biology
  • Pharmacology

Background:

  • Calcium-activated chloride channels (CaCC) are essential for numerous physiological processes, including Cl- secretion in epithelia and smooth muscle function.
  • Anoctamine 1 (ANO1 or TMEM16A) is the protein forming CaCC, and its dysregulation is linked to various pathologies such as cancer, hypertension, asthma, and cystic fibrosis.
  • TMEM16A interacts with key signaling pathways like EGFR, MAPK, and TGF-β, highlighting its central role in cellular functions and disease.

Purpose of the Study:

  • To review the known natural and synthetic compounds that modulate CaCC currents.
  • To summarize the effects of these compounds on pathologies associated with CaCC dysfunction.
  • To provide insights into potential therapeutic strategies targeting CaCC.

Main Methods:

  • Literature review of studies on CaCC modulators.
  • Analysis of the role of TMEM16A and its isoforms in physiological and pathophysiological conditions.
  • Summary of compound effects on CaCC activity and related diseases.

Main Results:

  • CaCC, primarily anoctamine 1 (TMEM16A), plays a significant role in epithelial secretion, vascular tone, and smooth muscle function.
  • TMEM16A is implicated in carcinogenesis, cancer cell proliferation, hypertension, asthma, cystic fibrosis, and gastrointestinal disorders.
  • Isoforms like ANO2, ANO6, and ANO5 are involved in olfaction, scrambling activity (Scott syndrome), and muscle/bone diseases, respectively.
  • Various natural and synthetic compounds have been identified that can block or modulate CaCC currents.

Conclusions:

  • CaCC, particularly TMEM16A, are critical targets for therapeutic intervention in a range of diseases.
  • Modulators of CaCC show promise for treating conditions including cancer, hypertension, and respiratory diseases.
  • Further research into CaCC-targeting compounds could lead to novel treatment strategies.