Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

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...
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,...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

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 include the...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

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 include the...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship01:16

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Role of TRPM4 ion channel in pediatric arrhythmic syndromes.

World journal of clinical pediatrics·2026
Same author

Missense mutation causes multiple defects in Nav1.4 channel gating and leads to an SCN4A-associated overlap phenotype.

The Journal of general physiology·2026
Same author

Functional characterization of voltage-gated sodium channels in two mirid pests and identification of kdr mutations in pyrethroid resistant Lygus lineolarispopulation.

Insect biochemistry and molecular biology·2026
Same author

How Sodium and Calcium Ions Pass Through Batrachotoxin-Bound Sodium Channel.

Toxins·2025
Same author

Predicting the Damaging Potential of Uncharacterized <i>KCNQ1</i> and <i>KCNE1</i> Variants.

International journal of molecular sciences·2025
Same author

Evolution of iGluR ligand specificity, polyamine regulation, and ion selectivity inferred from a placozoan epsilon receptor.

Communications biology·2025

Related Experiment Video

Updated: Jun 20, 2026

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
04:48

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate

Published on: July 10, 2018

Structural model for phenylalkylamine binding to L-type calcium channels.

Ricky C K Cheng1, Denis B Tikhonov2, Boris S Zhorov1

  • 1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.

The Journal of Biological Chemistry
|August 25, 2009
PubMed
Summary

Phenylalkylamines (PAAs) block L-type calcium channels (LTCCs) by binding to specific sites, including a Ca(2+) ion. This interaction explains drug potency and calcium potentiation, offering insights into drug design.

More Related Videos

Modeling Ligands into Maps Derived from Electron Cryomicroscopy
09:30

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Published on: July 19, 2024

One-channel Cell-attached Patch-clamp Recording
13:07

One-channel Cell-attached Patch-clamp Recording

Published on: June 9, 2014

Related Experiment Videos

Last Updated: Jun 20, 2026

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
04:48

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate

Published on: July 10, 2018

Modeling Ligands into Maps Derived from Electron Cryomicroscopy
09:30

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Published on: July 19, 2024

One-channel Cell-attached Patch-clamp Recording
13:07

One-channel Cell-attached Patch-clamp Recording

Published on: June 9, 2014

Area of Science:

  • Pharmacology
  • Structural Biology
  • Computational Chemistry

Background:

  • Phenylalkylamines (PAAs) are crucial L-type calcium channel (LTCC) blockers.
  • The precise structural basis of PAA-LTCC interactions is not fully understood.

Purpose of the Study:

  • To elucidate the structural mechanisms of PAA binding to LTCCs.
  • To explain structure-activity relationships and drug-channel interactions.

Main Methods:

  • Construction of a KvAP-based LTCC model.
  • Monte Carlo energy minimizations for docking PAAs (devapamil, verapamil, gallopamil).

Main Results:

  • PAA models reveal common binding features: H-bonds involving methoxy groups and Tyr residues, ammonium group stabilization, and nitrile group interaction with Ca(2+).
  • The Ca(2+) binding explains Ca(2+) potentiation of PAA action.
  • Models predict interactions with engineered Tyr residues, explaining enhanced drug potency.

Conclusions:

  • The developed PAA-LTCC models provide a mechanistic explanation for structure-activity relationships.
  • The findings clarify PAA access, LTCC mutation effects, and Ca(2+) potentiation.
  • Insights into commonalities and differences with other calcium channel blockers (dihydropyridines, benzothiazepines) are discussed.