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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,...
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,...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...

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Related Experiment Video

Updated: May 27, 2026

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography
07:51

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography

Published on: September 22, 2011

Ca2+/calmodulin-dependent protein kinase II function in vascular remodelling.

Harold A Singer1

  • 1Center for Cardiovascular Sciences, Albany Medical College (MC-8), 47 New Scotland Avenue, Albany, NY 12208, USA. singerh@mail.amc.edu

The Journal of Physiology
|November 30, 2011
PubMed
Summary
This summary is machine-generated.

Vascular smooth muscle cells switch phenotypes after injury, driven by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) signaling. CaMKIIδ activation promotes this transition and vascular remodeling.

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Area of Science:

  • Cardiovascular Biology
  • Molecular Cell Biology
  • Biochemistry

Background:

  • Vascular smooth muscle (VSM) cells undergo phenotypic switching post-injury, contributing to vascular wall remodeling.
  • This switch involves altered gene expression and intracellular Ca(2+) signaling, impacting cell proliferation, motility, and gene transcription.
  • The precise mechanisms linking Ca(2+) signaling to VSM remodeling remain unclear.

Purpose of the Study:

  • To review the role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in VSM phenotype switching and synthetic function.
  • To elucidate the mechanisms by which CaMKII influences VSM cell behavior and vascular remodeling.

Main Methods:

  • Review of existing literature on CaMKII function in VSM.
  • Analysis of in vivo studies showing changes in CaMKII isoform expression after vascular injury.
  • Examination of in vitro studies investigating CaMKII regulation of VSM proliferation, motility, and gene expression.

Main Results:

  • Vascular injury induces rapid changes in CaMKII isoform expression, notably upregulating CaMKIIδ in medial VSM.
  • Suppression of CaMKIIδ via siRNA or gene deletion attenuates VSM proliferation and neointimal formation.
  • In vitro studies demonstrate CaMKII's role in regulating VSM proliferation, motility, and gene expression through CREB1 and HDACIIa/MEF2 pathways.

Conclusions:

  • Ca(2+) signaling through CaMKIIδ is a key driver of VSM phenotype transitions.
  • CaMKIIδ promotes vascular remodeling by regulating VSM cell proliferation, motility, and gene expression.
  • Understanding CaMKII pathways offers potential therapeutic targets for vascular diseases.