Related Experiment Video

Updated: Mar 30, 2026

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
12:09

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

Published on: December 31, 2013

10.7K

Transient receptor potential (TRP) channels as a therapeutic target for intervention of respiratory effects and

Devon Andres1, Brian Keyser1, Betty Benton1

  • 1Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA.

Toxicology Letters
|November 13, 2015
PubMed

Insights

Phosgene exposure increases intracellular calcium in airway cells. Transient receptor potential (TRP) channel blockers prevented this effect, suggesting TRP channels are key targets for mitigating phosgene toxicity.

Area of Science:

  • Toxicology
  • Cell Biology
  • Respiratory Medicine

Background:

  • Phosgene (CG) is a toxic industrial gas causing life-threatening respiratory effects like bronchoconstriction.
  • Transient receptor potential (TRP) channels in the respiratory tract detect toxic inhalation hazards (TIH) and mediate harmful responses.
  • TRP channel activation by TIH can lead to broncho- and vasoconstriction.

Purpose of the Study:

  • To investigate the role of TRP channels in phosgene-induced intracellular calcium ([Ca(2+)]i) changes in human airway cells.
  • To evaluate the potential of TRP channel blockers as therapeutic interventions against phosgene toxicity.

Main Methods:

  • Human bronchial smooth muscle cells (BSMC) and pulmonary microvascular endothelial cells (HPMEC) were exposed to phosgene (16ppm, 8min) using an air/liquid interface system.
  • Intracellular free Ca(2+) concentration ([Ca(2+)]i) was measured.
  • Cells were treated with TRP channel blockers (SKF-96365 and RR) to assess their effects on CG-induced [Ca(2+)]i.

Main Results:

  • Phosgene exposure significantly increased [Ca(2+)]i in both BSMC and HPMEC.
  • The phosgene-induced increase in [Ca(2+)]i was significantly blocked by both a general TRP channel blocker (SKF-96365) and a TRPV blocker (RR).
  • These in vitro findings correlated with in vivo data showing protection against phosgene-induced lung injury and lethality in mice.

Conclusions:

  • TRP channels are involved in mediating phosgene-induced intracellular calcium signaling in human airway and endothelial cells.
  • TRP channel blockers show potential for therapeutic intervention against phosgene toxicity.
  • Targeting TRP channels represents a promising strategy to mitigate the harmful effects of phosgene inhalation.
Keywords:
Calcium signalingInhalationPhosgeneRespiratory toxicologySKFTRP channelsTherapeutic

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

10.0K
Purification of Endogenous Drosophila Transient Receptor Potential Channels08:39

Purification of Endogenous Drosophila Transient Receptor Potential Channels

Published on: December 28, 2021

2.3K

Related Concept Videos

Thermosensation01:43

Thermosensation

Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
35.4K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

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...
6.9K
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...
4.8K
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...
8.1K
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....
9.0K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
4.9K