Related Experiment Video

Updated: Nov 28, 2025

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
07:17

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels

Published on: December 13, 2024

1.4K

Inactivation-mimicking block of the epithelial calcium channel TRPV6

Rajesh Bhardwaj1, Sonja Lindinger2, Arthur Neuberger3

  • 1Department of Nephrology and Hypertension and Department of Biomedical Research, University of Bern, Inselspital, Freiburgstrasse 15, CH-3010 Bern, Switzerland.

Science Advances
|November 28, 2020
PubMed

Insights

Researchers discovered how specific compounds inhibit the epithelial calcium channel TRPV6. These PCHPDs block the channel pore, offering a new strategy for developing selective TRPV6-targeting drugs.

Area of Science:

  • Molecular biology
  • Structural biology
  • Pharmacology

Background:

  • Epithelial calcium channel TRPV6 is crucial for calcium homeostasis.
  • TRPV6 dysregulation is linked to various diseases, including cancers.

Purpose of the Study:

  • To elucidate the molecular mechanism of selective TRPV6 inhibition by (4-phenylcyclohexyl)piperazine derivatives (PCHPDs).
  • To identify inhibitor binding sites and understand the structural basis of PCHPDs' action.

Main Methods:

  • X-ray crystallography and cryo-electron microscopy to determine inhibitor-bound TRPV6 structures.
  • Mutagenesis, functional assays, and computational approaches to validate findings.

Main Results:

  • Identified two types of inhibitor binding sites: modulatory sites and a main site within the ion channel pore.
  • Demonstrated that PCHPDs plug the open TRPV6 pore, rendering the channel nonconducting.
  • Mechanism mimics calmodulin-induced inactivation of TRPV6.

Conclusions:

  • PCHPDs inhibit TRPV6 by physically blocking the ion pore, explaining their high selectivity and potency.
  • This biomimetic inhibition mechanism provides a foundation for designing novel TRPV6-targeting therapeutics.

More Related Videos

Controllable Ion Channel Expression through Inducible Transient Transfection10:00

Controllable Ion Channel Expression through Inducible Transient Transfection

Published on: February 17, 2017

9.7K
Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV412:09

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4

Published on: December 31, 2013

10.4K

Related Concept Videos

Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
1.3K
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

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...
3.4K
Depolarizing Blockers: Mechanism of Action01:28

Depolarizing Blockers: Mechanism of Action

Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
2.3K
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

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...
7.3K
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.7K
Non-gated Ion Channels01:24

Non-gated Ion Channels

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....
7.7K