TRPC4

TRPC4

Overview

TRPC4 (Transient Receptor Potential Cation Channel Subfamily C Member 4) is a non-selective calcium-permeable cation channel belonging to the TRPC (Transient Receptor Potential Canonical) family. It plays important roles in neuronal signaling, neuroprotection, and various brain functions.

Gene Information

<div class="infobox infobox-gene"> [@diacylglycerol2003]
<table> [@trpc2008]
<tr><th>Symbol</th><td>TRPC4</td></tr> [@trpc2009]
<tr><th>Full Name</th><td>Transient Receptor Potential Cation Channel Subfamily C Member 4</td></tr> [@calmodulin2001]
<tr><th>Chromosomal Location</th><td>Chromosome 13q13.3</td></tr> [@trpc2014]
<tr><th>NCBI Gene ID</th><td>[7224](https://www.ncbi.nlm.nih.gov/gene/7224)</td></tr> [@trpc2010]
<tr><th>OMIM</th><td>[603299](https://www.omim.org/entry/603299)</td></tr> [@trpc2016]
<tr><th>Ensembl ID</th><td>ENSG00000133189</td></tr> [@trpc2009a]
<tr><th>UniProt ID</th><td>[Q9H9N0](https://www.uniprot.org/uniprot/Q9H9N0)</td></tr> [@trpc2012]
<tr><th>Associated Diseases</th><td>Neurodevelopmental disorders, Epilepsy, Anxiety disorders</td></tr> [@trpc2009b]
</table> [@trpc2018]
</div> [@trpc2014a]

Function

TRPC4 forms non-selective cation channels that are primarily activated by G-protein-coupled receptor (GPCR) signaling through phospholipase C (PLC). The channel conducts Ca²⁺ and Na⁺ ions, leading to membrane depolarization and activation of downstream signaling cascades [1](https://pubmed.ncbi.nlm.nih.gov/14534157/). [@trpc2009c]

TRPC4

Overview

TRPC4 (Transient Receptor Potential Cation Channel Subfamily C Member 4) is a non-selective calcium-permeable cation channel belonging to the TRPC (Transient Receptor Potential Canonical) family. It plays important roles in neuronal signaling, neuroprotection, and various brain functions.

Gene Information

<div class="infobox infobox-gene"> [@diacylglycerol2003]
<table> [@trpc2008]
<tr><th>Symbol</th><td>TRPC4</td></tr> [@trpc2009]
<tr><th>Full Name</th><td>Transient Receptor Potential Cation Channel Subfamily C Member 4</td></tr> [@calmodulin2001]
<tr><th>Chromosomal Location</th><td>Chromosome 13q13.3</td></tr> [@trpc2014]
<tr><th>NCBI Gene ID</th><td>[7224](https://www.ncbi.nlm.nih.gov/gene/7224)</td></tr> [@trpc2010]
<tr><th>OMIM</th><td>[603299](https://www.omim.org/entry/603299)</td></tr> [@trpc2016]
<tr><th>Ensembl ID</th><td>ENSG00000133189</td></tr> [@trpc2009a]
<tr><th>UniProt ID</th><td>[Q9H9N0](https://www.uniprot.org/uniprot/Q9H9N0)</td></tr> [@trpc2012]
<tr><th>Associated Diseases</th><td>Neurodevelopmental disorders, Epilepsy, Anxiety disorders</td></tr> [@trpc2009b]
</table> [@trpc2018]
</div> [@trpc2014a]

Function

TRPC4 forms non-selective cation channels that are primarily activated by G-protein-coupled receptor (GPCR) signaling through phospholipase C (PLC). The channel conducts Ca²⁺ and Na⁺ ions, leading to membrane depolarization and activation of downstream signaling cascades [1](https://pubmed.ncbi.nlm.nih.gov/14534157/). [@trpc2009c]

Key functional characteristics:

• Gating Mechanism: Activated by diacylglycerol (DAG) and mechanical stretch [2](https://pubmed.ncbi.nlm.nih.gov/12677012/)
• Expression Pattern: Widely expressed in the brain, particularly in hippocampal [neurons](/entities/neurons), cortical pyramidal cells, and cerebellar granule cells [3](https://pubmed.ncbi.nlm.nih.govPMC2920347/)
• Physiological Roles: Regulation of neuronal excitability, neurotransmitter release, synaptic plasticity, and neuroprotection [4](https://pubmed.ncbi.nlm.nih.gov/19749643/)
• Interaction Partners: Associates with TRPC5 to form heteromeric channels, interacts with calmodulin and PLC isoforms [5](https://pubmed.ncbi.nlm.nih.gov/11025714/)

Disease Associations

Neurological Disorders

• Epilepsy: TRPC4 variants have been linked to idiopathic generalized epilepsy [6](https://pubmed.ncbi.nlm.nih.gov/23472105/)
• Anxiety Disorders: Reduced TRPC4 expression associated with anxiety-like behaviors in mouse models [7](https://pubmed.ncbi.nlm.nih.gov/20167575/)
• Neurodevelopmental Disorders: De novo mutations identified in patients with intellectual disability [8](https://pubmed.ncbi.nlm.nih.gov/28554332/)

Neuroprotection

• Ischemic Stroke: TRPC4 activation mediates neuroprotective signaling in cerebral ischemia [9](https://pubmed.ncbi.nlm.nih.gov/19349363/)
• Parkinson's Disease: Altered TRPC4 expression in dopaminergic neurons may affect neuronal survival [10](https://pubmed.ncbi.nlm.nih.gov/22154924/)

Expression in the Brain

TRPC4 shows high expression in:

• [Hippocampus](/brain-regions/hippocampus): CA1-CA3 pyramidal neurons, dentate gyrus granule cells
• Cerebral [Cortex](/brain-regions/cortex): Layer II-IV pyramidal neurons
• Cerebellum: Granule cells and Purkinje cells
• Thalamus: Relay neurons

Therapeutic Implications

TRPC4 represents a potential therapeutic target for:

• Anxiety and Depression: TRPC4 agonists may have anxiolytic effects [12](https://doi.org/10.1016/j.neuropharm.2018.03.014)
• Epilepsy: Modulation of TRPC4 activity may reduce seizure frequency [13](https://pubmed.ncbi.nlm.nih.gov/23472105/)
• Ischemic Neuroprotection: TRPC4 activators could protect neurons during stroke [14](https://pubmed.ncbi.nlm.nih.gov/19349363/)

See Also

• [TRPC5](/genes/trpc5) - Related TRP channel
• [TRPC6](/genes/trpc6) - Related TRP channel
• [Calcium Signaling](/mechanisms/calcium-signaling)mechanisms/calcium-signaling-dysregulation) - Calcium homeostasis
• [Ion Channels](/mechanisms/ion-channels) - Neuronal ion channels

External Links

• [NCBI Gene: trpc4](https://www.ncbi.nlm.nih.gov/gene/)
• [PubMed: trpc4](https://pubmed.ncbi.nlm.nih.gov/?term=trpc4+neurodegeneration)

References