Related Experiment Video
Updated: May 20, 2026
10:46
Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
Published on: July 16, 2013
Low extracellular Ca2+ conditions induce an increase in brain endothelial permeability that involves intercellular
Marijke De Bock1, Maxime Culot, Nan Wang
1Department of Basic Medical Sciences, Physiology Group, Ghent University, De Pintelaan 185, Building B, 9000 Ghent, Belgium.
Brain Research
|July 14, 2012
Summary
Spatially propagated intercellular calcium waves (ICWs) significantly increase endothelial permeability, including the blood-brain barrier (BBB). Connexin channels mediating these waves are potential targets for limiting BBB dysfunction.
Area of Science:
- Endothelial Biology
- Cellular Physiology
- Neuroscience
Background:
- Intracellular calcium concentration ([Ca(2+)](i)) regulates endothelial barrier function, including the blood-brain barrier (BBB).
- The role of intercellular calcium waves (ICWs) in endothelial permeability remains largely unknown.
- Connexins, crucial for ICW propagation, are present in endothelial cells.
Purpose of the Study:
- To investigate the impact of ICWs on endothelial permeability.
- To compare the effects of ICWs with bradykinin (BK)-induced permeability changes.
- To identify molecular pathways involved in ICW-mediated endothelial barrier disruption.
Main Methods:
- Triggering ICW activity in brain endothelial cells by altering extracellular calcium.
- Measuring endothelial permeability changes.
- Utilizing calcium buffering (BAPTA-AM), connexin channel blockers (Gap27), and inhibitors of protein kinase C (PKC), Ca(2+)/calmodulin-dependent kinase II (CaMKII), and actomyosin contraction.
- Comparing ICW effects with bradykinin (BK)-induced responses.
Main Results:
- Lowering extracellular calcium induced ICWs and significantly increased endothelial permeability.
- Calcium buffering and Gap27 treatment suppressed ICW-induced permeability increases.
- Inhibition of PKC, CaMKII, and actomyosin contraction also reduced permeability.
- ICW-induced permeability increases were substantially greater than those caused by BK.
- BK-induced permeability was not affected by inhibition of PKC, CaMKII, or actomyosin contraction.
Conclusions:
- Intercellular calcium waves (ICWs) significantly enhance endothelial permeability.
- Connexin channels are key mediators of ICW propagation and subsequent barrier disruption.
- Targeting connexin channels may offer a strategy to mitigate blood-brain barrier (BBB) alterations.
More Related Videos
Related Concept Videos
01:22Cerebral Edema ll: Pathophysiology
Vasogenic edema is a major form of cerebral edema characterized by abnormal accumulation of fluid in the brain’s extracellular space due to disruption of the blood–brain barrier (BBB). The BBB is a specialized structure composed of endothelial cells connected by tight junctions, supported by astrocytic endfeet and a basement membrane. Under normal conditions, it tightly regulates the movement of ions, proteins, and solutes between the bloodstream and brain parenchyma. When this barrier loses...
01:27Feedback 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...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:19Cerebral Edema l: Introduction
Cerebral edema is a pathological increase in brain water content that disrupts intracranial pressure regulation and impairs neurological function. Because the cranial vault is rigid, even modest increases in tissue volume can compromise cerebral perfusion, distort neural structures, and initiate secondary injury. Cerebral edema develops through four principal mechanisms: vasogenic, cytotoxic, interstitial, and ionic.Vasogenic EdemaVasogenic edema arises from disruption of the blood–brain...
01:21Cytotoxic Edema: Pathophysiology
Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...
01:29Increased Intracranial Pressure ll: Pathophysiology
Increased intracranial pressure (ICP) refers to a potentially life-threatening rise in pressure inside the skull. This usually happens when there is a major change in the volume of brain tissue, blood, or cerebrospinal fluid (CSF) — the three components inside the skull. According to the Monro-Kellie doctrine, if the volume of one component increases, the volumes of the other components must decrease to maintain normal pressure. If this does not happen, ICP rises.The process often begins with...
00:49The Blood-brain Barrier
Overview