Mechanisms of capacitative calcium entry
J W Putney1, L M Broad, F J Braun
1Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, Research Triangle, Park, NC 27709, USA. putney@niehs.nih.gov
Journal of Cell Science
|August 9, 2001
Summary
Capacitative calcium entry into cells is regulated by endoplasmic reticulum store filling. While conformational coupling via inositol 1,4,5-trisphosphate receptors is one theory, evidence suggests multiple signaling mechanisms may exist.
Area of Science:
- Cellular Physiology
- Molecular Biology
- Calcium Signaling
Background:
- Capacitative calcium entry (CCE) links endoplasmic reticulum (ER) Ca(2+) store status to plasma membrane Ca(2+) channel activity.
- The precise mechanism of communication between ER stores and plasma membrane Ca(2+) channels remains under investigation.
- Inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) receptors are implicated in sensing store Ca(2+) levels.
Purpose of the Study:
- To investigate the role of inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) receptors in mediating capacitative calcium entry (CCE).
- To explore potential mechanisms, including conformational coupling and diffusible signals, in CCE regulation.
- To reconcile conflicting evidence regarding the involvement of Ins(1,4,5)P(3) receptors in CCE.
Main Methods:
- Electrophysiological recordings of capacitative calcium entry currents.
- Pharmacological inhibition of phospholipase C and phosphatidylinositol 4-kinase.
- Studies using Ins(1,4,5)P(3) receptor antagonists and gene-disrupted cells.
Main Results:
- Store-operated channels in excised patches sometimes require Ins(1,4,5)P(3) and its receptors for activity.
- Inhibitors of Ins(1,4,5)P(3) production block CCE, but CCE currents are not blocked by Ins(1,4,5)P(3) receptor antagonists.
- Cells lacking Ins(1,4,5)P(3) receptor genes can still activate CCE channels upon store depletion.
Conclusions:
- Conflicting results suggest that Ins(1,4,5)P(3) receptors are not universally required for capacitative calcium entry.
- Conformational coupling involving Ins(1,4,5)P(3) receptors may operate in some cell types.
- Alternative signaling pathways, potentially involving diffusible factors, likely contribute to CCE in other cell types.
Related Concept Videos
01:19The 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.
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.
01:12Mechanically-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...
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...
01:16Calmodulin-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 Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:30Ligand-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...
01:12Mechanically-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...