Related Experiment Video
Updated: Jun 22, 2026
06:05
Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx
Published on: May 2, 2025
Calpain and the glutamatergic synapse
1Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Frontiers in Bioscience (Scholar Edition)
|June 2, 2009
Summary
Calpain protease regulates neuronal function by cleaving glutamate receptors, impacting synaptic transmission. This protease may play roles in both neuroprotection and excitotoxicity.
Area of Science:
- Neuroscience
- Molecular Biology
- Enzymology
Background:
- Calpains are ubiquitous proteases present in various tissues and organisms.
- Calpains typically disrupt substrate function rather than destroy them.
- In neurons, calpain cleavage of regulatory domains dysregulates substrates, altering cell signaling.
Purpose of the Study:
- To investigate the role of calpain in neuronal function and synaptic transmission.
- To identify calpain's substrates within glutamatergic synapses.
- To explore the dual role of calpain in both pathological and physiological neuronal processes.
Main Methods:
- Analysis of calpain activity in neuronal tissues.
- Identification of calpain substrates, including glutamate receptors.
- Investigation of the functional consequences of calpain-mediated cleavage.
Main Results:
- Calpain directly targets major glutamate receptors (NMDA, AMPA, mGluR) in glutamatergic synapses.
- Cleavage of these receptors and associated proteins by calpain influences synaptic physiology.
- Calpain-mediated cleavage affects neuronal signaling pathways.
Conclusions:
- Calpain plays a significant role in regulating glutamatergic synaptic transmission.
- Calpain activity in neurons is implicated in excitotoxicity.
- Calpain may also exert neuroprotective effects and contribute to normal synaptic function.
Related Concept Videos
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...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
02:47The Synapse
Neurons communicate with one another by passing on their electrical signals to other neurons. A synapse is the location where two neurons meet to exchange signals. At the synapse, the neuron that sends the signal is called the presynaptic cell, while the neuron that receives the message is called the postsynaptic cell. Note that most neurons can be both presynaptic and postsynaptic, as they both transmit and receive information.
01:19Ligand-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...
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...