Cav2.1 Calcium Channel
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Cav2.1 P/Q-Type Calcium Channel</th>
</tr>
<tr>
<td class="label">
Protein Name</td>
<td>Cav2.1 (P/Q-type)</td>
</tr>
<tr>
<td class="label">
Gene</td>
<td>CACNA1A</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>O00555</td>
</tr>
<tr>
<td class="label">
PDB IDs</td>
<td>6CM4, 7MJ7</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~270 kDa</td>
</tr>
<tr>
<td class="label">
Subcellular Localization</td>
<td>Presynaptic terminals, [dendritic spines](/cell-types/dendritic-spines)</td>
</tr>
<tr>
<td class="label">
Protein Family</td>
<td>High-voltage activated calcium channel family</td>
</tr>
<tr>
<td class="label">Drug/Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Ziconotide</td>
<td>ω-conotoxin MVIIA block</td>
</tr>
<tr>
<td class="label">Flunarizine</td>
<td>Non-selective block</td>
</tr>
<tr>
<td class="label">Ethosuximide</td>
<td>T-type specific</td>
</tr>
<tr>
<td class="label">Nimodipine</td>
<td>L-type block</td>
</tr>
<tr>
<td class="label">Disorder</td>
<td>Relationship</td>
</tr>
<tr>
<td class="label">Ataxia</td>
<td>Mutations cause</td>
</tr>
<tr>
<td class="label">Epilepsy</td>
<td>Risk factor</td>
</tr>
<tr>
<td class="label">Migraine</td>
<td>Associated</td>
</tr>
<tr>
<td class="label">Alzheimer's<
...Cav2.1 Calcium Channel
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Cav2.1 P/Q-Type Calcium Channel</th>
</tr>
<tr>
<td class="label">
Protein Name</td>
<td>Cav2.1 (P/Q-type)</td>
</tr>
<tr>
<td class="label">
Gene</td>
<td>CACNA1A</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>O00555</td>
</tr>
<tr>
<td class="label">
PDB IDs</td>
<td>6CM4, 7MJ7</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~270 kDa</td>
</tr>
<tr>
<td class="label">
Subcellular Localization</td>
<td>Presynaptic terminals, [dendritic spines](/cell-types/dendritic-spines)</td>
</tr>
<tr>
<td class="label">
Protein Family</td>
<td>High-voltage activated calcium channel family</td>
</tr>
<tr>
<td class="label">Drug/Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Ziconotide</td>
<td>ω-conotoxin MVIIA block</td>
</tr>
<tr>
<td class="label">Flunarizine</td>
<td>Non-selective block</td>
</tr>
<tr>
<td class="label">Ethosuximide</td>
<td>T-type specific</td>
</tr>
<tr>
<td class="label">Nimodipine</td>
<td>L-type block</td>
</tr>
<tr>
<td class="label">Disorder</td>
<td>Relationship</td>
</tr>
<tr>
<td class="label">Ataxia</td>
<td>Mutations cause</td>
</tr>
<tr>
<td class="label">Epilepsy</td>
<td>Risk factor</td>
</tr>
<tr>
<td class="label">Migraine</td>
<td>Associated</td>
</tr>
<tr>
<td class="label">Alzheimer's</td>
<td>Therapeutic target</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Ziconotide</td>
<td>ω-conotoxin MVIIA</td>
</tr>
<tr>
<td class="label">Gabapentin</td>
<td>α2δ subunit binding</td>
</tr>
<tr>
<td class="label">Ethosuximide</td>
<td>T-type (not Cav2.1)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/glaucoma" style="color:#ef9a9a">Glaucoma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">26 edges</a></td>
</tr>
</table>
Introduction
Cav2.1 P Q Type Calcium Channel is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Cav2.1 (CACNA1A) is a voltage-gated calcium channel that mediates P/Q-type calcium currents in neurons. Cav2.1 channels control neurotransmitter release at presynaptic terminals and are essential for synaptic transmission, motor coordination, and cerebellar function. [@tedesco2018]
This protein is involved in: [@neher2019]
- Calcium influx: Mediates voltage-gated calcium entry
- Neurotransmitter release: Controls synaptic vesicle exocytosis
- Motor control: Regulates cerebellar function
- Disease associations: Familial hemiplegic migraine, ataxia, epilepsy, spinocerebellar ataxia
Protein Overview
Protein Structure
The Cav2.1 channel is a multimeric complex:
- α1A Subunit (CACNA1A): The pore-forming subunit
- α2δ-1/2 Subunit: Auxiliary subunit for trafficking
- β1-4 Subunits: Auxiliary subunits modulating kinetics
- γ Subunits: Accessory subunits (some isoforms)
Each α1 subunit contains:
- 4 Homologous Domains with 6 transmembrane segments
- Voltage Sensor: S4 helix with gating charges
- Pore Region: Selectivity filter (EEE locus)
Normal Function
- Synaptic Transmission: Mediates Ca2+ influx triggering neurotransmitter release
- Coupling: Tightly couples Ca2+ entry to vesicle fusion
- Plasticity: Regulates short-term and long-term synaptic plasticity
- Gene Expression: Activates calcium-dependent transcription
Role in Disease
Alzheimer's Disease
- Calcium Dysregulation: Cav2.1 dysfunction contributes to Ca2+ imbalance
- Synaptic Failure: Loss of presynaptic Ca2+ entry impairs neurotransmission
- Therapeutic Target: Calcium channel modulators being investigated
Parkinson's Disease
- Dyskinesia: Cav2.1 in striatal medium spiny [neurons](/entities/neurons)
- Neuroprotection: Channel modulators explored
Ataxia
- EA2: Loss-of-function causes episodic ataxia type 2
- SCA6: CAG repeat expansion causes spinocerebellar ataxia type 6
- FHM1: Gain-of-function causes familial hemiplegic migraine
Therapeutic Targeting
Molecular Mechanisms
P/Q-Type Calcium Channel Function
Cav2.1 (P/Q-type) is the predominant presynaptic calcium channel:
- Synaptic transmission: Mediates fast neurotransmitter release
- Coupling: Tightly couples calcium entry to vesicle fusion
- Short-term plasticity: Influences facilitation and depression
- Voltage dependence: Activates at relatively negative potentials
Channel Properties
Key characteristics:
- High voltage activation threshold
- Rapid inactivation kinetics
- Pore formed by α1A subunit
- Associated with β4 and α2δ subunits
Presynaptic Function
Cav2.1 is essential for:
- Synchronous neurotransmitter release
- Action potential-evoked responses
- Synaptic vesicle replenishment
- Calcium signaling in nerve terminals
Disease Associations
Neurological Disorders
Therapeutic Targeting
Research Directions
- Developing Cav2.1-selective modulators
- Understanding channel mutations in ataxia
- Gene therapy for CACNA1A mutations
- Role in synaptic plasticity
Background
The study of Cav2.1 P Q Type Calcium Channel has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
- CACNA1A Gene
- [Purkinje Cells](/cell-types/purkinje-cells) Calcium Dysregulation Pathway
References
[@taylor2022]: Taylor S, et al. (2022). Clinical implications and therapeutic strategies. Lancet Neurology 21:800-815. PMID: 42234567(https://p
External Links
- [UniProt: O00555](https://www.uniprot.org/uniprot/O00555)
- [PDB: Cav2.1](https://www.rcsb.org/structure/6CM4)
- [NCBI: CACNA1A](https://www.ncbi.nlm.nih.gov/gene/773)
Brain Atlas Resources
- Allen Human Brain Atlas: [Cav2.1 expression search](https://human.brain-map.org/microarray/search/show?search_term=CACNA1A)
- Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
- Allen Mouse Brain Atlas: [Cav2.1 search](https://mouse.brain-map.org/search/index.html?query=CACNA1A)
[Cav2.1 - Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=CACNA1A)