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Related Concept Videos

Non-gated Ion Channels01:24

Non-gated Ion Channels

7.8K
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....
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Patch Clamp01:18

Patch Clamp

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Many fundamental cell functions such as muscle contraction and nerve transmission rely on the electrical signals produced by the movement of positively and negatively charged ions across the cell membrane. One competent method to record current flowing across the whole cell or single ion channel is the patch-clamp technique.
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
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Electrochemical Gradient and Channel Proteins: An Overview01:21

Electrochemical Gradient and Channel Proteins: An Overview

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An electrochemical gradient is a fundamental concept in biology and chemistry. It regulates the movement of ions across cell membranes. This movement is influenced by two factors:
The electrical gradient: The electrical gradient across cell membranes refers to the difference in electric charge between the inside and outside of a cell.  This difference drives the movement of ions towards or away from the cells. For instance, if the inside of the cell is more negatively charged relative to...
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Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

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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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Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

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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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Pore Transport and Ion-Pair Transport01:17

Pore Transport and Ion-Pair Transport

1000
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited  but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
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Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution
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Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution

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Targeting Two-Pore Channels: Current Progress and Future Challenges.

Xuhui Jin1, Yuxuan Zhang1, Abeer Alharbi1

  • 1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK.

Trends in Pharmacological Sciences
|July 18, 2020
PubMed
Summary
This summary is machine-generated.

Two-pore channels (TPCs) are crucial for calcium signaling and implicated in diseases like cancer. Understanding TPC activation and developing direct modulators are key for future therapeutic strategies.

Keywords:
NAADPcalciumcell signallingendolysosomesinteractometwo-pore channels

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Area of Science:

  • Cellular Biology
  • Molecular Physiology
  • Pharmacology

Background:

  • Two-pore channels (TPCs) are endolysosomal cation channels vital for intracellular calcium (Ca2+) signaling.
  • TPCs influence critical cellular processes including growth, metabolism, and cancer progression.
  • Current research limitations include reliance on indirect inhibitors (Ned-19) and TPC knockout models, hindering mechanistic understanding.

Purpose of the Study:

  • To review recent advancements in understanding TPC structure, function, and activation mechanisms.
  • To discuss the development of direct pharmacological modulators for TPCs.
  • To highlight the therapeutic potential of targeting TPCs.

Main Methods:

  • Review of recent structural biology studies on TPCs.
  • Analysis of interactome data to identify TPC-interacting proteins.
  • Compilation of data on existing and emerging pharmacological modulators of TPCs.

Main Results:

  • Recent structural insights are facilitating the development of direct TPC modulators.
  • Understanding TPC activation mechanisms remains a significant challenge.
  • Targeting TPCs therapeutically is an emerging but promising area.

Conclusions:

  • Advances in TPC structural biology and interactome studies are paving the way for novel drug development.
  • Direct pharmacological modulation of TPCs holds significant therapeutic potential.
  • Further research is essential to fully elucidate TPC function and enable targeted therapies.