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

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 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...
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...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

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

The Role of Ion Channels in Neuronal Computation

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.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.

You might also read

Related Articles

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

Sort by
Same author

Ca<sub>V</sub>1.2 dynamics in native male arterial myocytes.

The Journal of physiology·2026
Same author

Context-Dependent Control: PKA Regulation of Vascular Ca<sub>V</sub>1.2 Requires S1928 not Rad Phosphorylation.

Arteriosclerosis, thrombosis, and vascular biology·2026
Same author

Phosphoinositide Depletion and Compensatory Phospho-Signaling in Angiotensin II-Induced Heart Disease.

Circulation research·2026
Same author

Disruption of the PIKfyve complex unveils an adaptive mechanism to promote lysosomal repair and mitochondrial homeostasis.

Nature communications·2025
Same author

Bend it like BIN1: how a membrane-curving adaptor protein shapes cardiac physiology.

American journal of physiology. Heart and circulatory physiology·2025
Same author

14-3-3 proteins: Regulators of cardiac excitation-contraction coupling and stress responses.

The Journal of physiology·2025

Related Experiment Video

Updated: May 18, 2026

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
10:30

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles

Published on: October 15, 2014

L-type Ca2+ channel function during Timothy syndrome.

Rose E Dixon1, Edward P Cheng, Jose L Mercado

  • 1Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.

Trends in Cardiovascular Medicine
|September 25, 2012
PubMed
Summary
This summary is machine-generated.

Mutations in cardiac calcium channels (Ca(v)1.2) cause Timothy syndrome by slowing channel closing. This leads to excessive calcium entry, prolonging heartbeats and increasing arrhythmia risk.

More Related Videos

Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry
11:32

Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry

Published on: September 28, 2016

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
09:36

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia

Published on: December 22, 2023

Related Experiment Videos

Last Updated: May 18, 2026

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
10:30

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles

Published on: October 15, 2014

Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry
11:32

Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry

Published on: September 28, 2016

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
09:36

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia

Published on: December 22, 2023

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Channelopathies

Background:

  • L-type Ca(2+) channels (Ca(v)1.2) are crucial for cardiac function, regulating action potentials and excitation-contraction coupling.
  • Specific mutations (G406R, G402S) in Ca(v)1.2 cause Timothy syndrome, a rare multisystem disorder.
  • These mutations are linked to altered channel kinetics and increased calcium influx.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying the slowed inactivation of Ca(v)1.2 channels in Timothy syndrome.
  • To investigate the role of scaffolding proteins in modulating the activity of mutant Ca(v)1.2 channels.
  • To propose a model explaining how TS mutations amplify calcium influx in cardiac myocytes.

Main Methods:

  • Analysis of Ca(v)1.2 channel function with Timothy syndrome mutations.
  • Investigating the interaction between Ca(v)1.2 channels and the scaffolding protein AKAP79/150.
  • Modeling the impact of mutations and protein interactions on channel activity and calcium dynamics.

Main Results:

  • Ca(v)1.2 channels with Timothy syndrome mutations exhibit significantly slowed inactivation, leading to prolonged calcium influx.
  • The scaffolding protein AKAP79/150 stabilizes the open state of mutant Ca(v)1.2 channels.
  • AKAP79/150 facilitates inter-channel interactions, amplifying calcium influx and cardiac action potential duration.

Conclusions:

  • Slowed inactivation of Ca(v)1.2 channels is a key mechanism in Timothy syndrome pathogenesis.
  • AKAP79/150 plays a critical role in stabilizing mutant Ca(v)1.2 channels and exacerbating calcium overload.
  • This provides a framework for understanding how channelopathies can lead to severe cardiac arrhythmias.