L Type Calcium Channel Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
L-type calcium channels (Cav1.2 and Cav1.3, encoded by CACNA1C and CACNA1D) are voltage-gated calcium channels that mediate calcium influx in response to depolarization, critical for neuronal signaling, gene expression, and synaptic plasticity.
This page provides comprehensive information about the protein/gene, its function in the nervous system, and its role in neurodegenerative diseases.
| Property |
Value |
| Protein Names |
Cav1.2 (CACNA1C), Cav1.3 (CACNA1D) |
| Gene Encoding |
CACNA1C (Cav1.2), CACNA1D (Cav1.3) |
| UniProt IDs |
Q13936 (Cav1.2), Q15878 (Cav1.3) |
| Molecular Weight |
~250 kDa per α1 subunit |
| Subcellular Localization |
Dendrites, soma, dendritic spines, some presynaptic terminals |
| Protein Family |
Voltage-gated calcium channels (Cav1/L-type) |
| Channel Stoichiometry |
α1 + β + α2δ + γ subunits |
L-type calcium channels are heteromultimeric complexes:
- α1 subunit: Forms the channel pore (Cav1.2 or Cav1.3)
- β subunit: Regulatory (β1-4, tissue-specific)
- α2δ subunit: Auxiliary, affects trafficking (α2δ1-4)
- γ subunit: Some tissues (Cavγ1-8)
- Four homologous domains (I-IV), each with 6 transmembrane segments
- S4 voltage sensor: Positively charged residues
- Pore loop: Selectivity filter (EEEE motif)
- C-terminal: Multiple regulatory domains
- Depolarization-triggered Ca2+ entry: Opens with membrane depolarization
- Long-lasting current: Name "L-type" = Long-lasting
- High voltage-activated: Activates at relatively positive potentials
- Slow inactivation: Inactivates slowly compared to other VGCCs
- Gene expression: Ca2+-dependent transcription (CREB)
- Synaptic plasticity: LTP in some brain regions
- Dendritic spikes: Back-propagating action potentials
- Cardiac muscle: Primary L-type channel in heart
- Lower voltage activation: More negative than Cav1.2
- Auditory system: Cochlear inner hair cells
- Neuroendocrine: Hormone release
- Parkinsonian neurons: More vulnerable to dysfunction
- Dysregulated Ca2+: "Calcium hypothesis" of AD
- Amyloid effects: Aβ modulates L-type channel function
- Excitotoxicity: Excessive Ca2+ entry
- Therapeutic target: L-type blockers investigated
- Gene variants: CACNA1C variants affect AD risk
- Cav1.3 vulnerability: Early dysfunction in dopaminergic neurons
- Calcium dysregulation: Contributes to selective vulnerability
- Therapeutic: Cav1.3 blockers (e.g., isradipine) being tested
- Parkinsonism: Some CACNA1C mutations cause parkinsonism
- CACNA1C mutations: Cause multisystem disorder
- Cardiac: Long QT, arrhythmias
- Neurological: Autism, intellectual disability
- Severe phenotype: Often lethal
- Bipolar disorder: CACNA1C is a major risk gene
- Schizophrenia: Some association
- Mechanism: Altered neuronal excitability and plasticity
- Dihydropyridines: Nifedipine, amlodipine, nicardipine
- Phenylalkylamines: Verapamil
- Benzothiazepines: Diltiazem
- Uses: Hypertension, angina, some arrhythmias
- Cav1.3-selective blockers: For PD (isradipine trial)
- Calcium channel agonists: For cognition
- Gene therapy: Under development
- L-type calcium channel structure (2019). Science. PMID:31806838
- Cav1.3 in Parkinson's disease (2018). Nature Reviews Neurology. PMID:29980753
- CACNA1C and psychiatric disorders (2020). Molecular Psychiatry. PMID:32080385
- Calcium hypothesis of AD (2021). Nature Reviews Neuroscience. PMID:34017082
The study of L Type Calcium Channel Protein 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.
[1] Zamponi GW, et al. Calcium channel subtypes: does the subtype match the therapeutic target? Nat Rev Drug Discov. 2015;14(9):590-591. PMID:26323542.
[2] Ertel EA, et al. Nomenclature of voltage-gated calcium channels. Neuron. 2000;25(3):533-535. PMID:10770706.
[3] Dolphin AC. Calcium channel auxiliary α2δ and β subunits: trafficking and therapeutic potential. Nat Rev Neurosci. 2023;24(4):213-225. PMID:36906765.
[4] Striessnig J, et al. Role of voltage-gated L-type Ca2+ channel subtypes in neurodegenerative diseases. Eur J Pharmacol. 2021;904:174188. PMID:33773999.
[5] Simms BA, et al. Calcium channelopathies and neurological disease. Brain Res. 2019;1707:160-172. PMID:30465721.
- Catterall WA (2011). "Voltage-gated calcium channels." Cold Spring Harbor Perspectives in Biology. PMID:21746798
- Striessnig J, et al. (2014). "L-type calcium channels." Handbook of Experimental Pharmacology. PMID:25233070
- Benarroch EE (2013). "L-type Ca2+ channels in neurological disease." Neurology. PMID:23553478
- Zhang Y, et al. (2019). "Cav1.2 channels in neurodegeneration." Neurobiology of Disease. PMID:30658899
Last updated: 2026-03-04