CACNA1C Gene

CACNA1C Gene

Introduction

Pathway Diagram

```mermaid
flowchart TD
CACNA1C["CACNA1C L-type Calcium Channel"]
Ca_influx["Calcium Influx"]
Ca_signaling["Calcium Signaling"]
Oxidative_phos["Oxidative Phosphorylation"]
Mitochondrial_dysfx["Mitochondrial Dysfunction"]
Inflammation["Neuroinflammation"]
Wnt_pathway["Wnt Signaling"]
Neurogenesis["Neurogenesis"]
Alzheimer["Alzheimer Disease"]
ALS_inhib["ALS Inhibition"]
MS_assoc["Multiple Sclerosis"]
Anxiety_disorder["Anxiety Disorders"]
Neurodegeneration["Neurodegeneration"]

CACNA1C -->|"mediates"| Ca_influx
Ca_influx -->|"activates"| Ca_signaling
Ca_signaling -->|"regulates"| Oxidative_phos
Oxidative_phos -->|"dysfunction leads to"| Mitochondrial_dysfx
CACNA1C -->|"promotes"| Inflammation
CACNA1C -->|"modulates"| Wnt_pathway
Wnt_pathway -->|"controls"| Neurogenesis
CACNA1C -->|"inhibits"| Neurogenesis
CACNA1C -->|"associated with"| Alzheimer
CACNA1C -->|"inhibits"| ALS_inhib
CACNA1C -->|"linked to"| MS_assoc
CACNA1C -->|"contributes to"| Anxiety_disorder
Mitochondrial_dysfx -->|"drives"| Neurodegeneration
Inflammation -->|"accelerates"| Neurodegeneration
Alzheimer -->|"leads to"| Neurodegeneration

classDef central fill:#006494
classDef protective fill:#1b5e20
classDef pathological fill:#ef5350
classDef regulatory fill:#4a1a6b
classDef outcome fill:#5d4400

CACNA1C Gene

Introduction

Pathway Diagram

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CACNA1C Gene</th>
</tr>
<tr>
<td class="label">Drug</td>
<td>Use</td>
</tr>
<tr>
<td class="label">Amlodipine</td>
<td>Hypertension, angina</td>
</tr>
<tr>
<td class="label">Nifedipine</td>
<td>Hypertension</td>
</tr>
<tr>
<td class="label">Verapamil</td>
<td>Arrhythmia, migraine</td>
</tr>
<tr>
<td class="label">Nimodipine</td>
<td>Subarachnoid hemorrhage</td>
</tr>
<tr>
<td class="label">Isradipine</td>
<td>Parkinson's disease</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">104 edges</a></td>
</tr>
</table>

Cacna1C Gene 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

CACNA1C encodes the alpha-1C subunit of the L-type voltage-gated calcium channel (Cav1.2), one of the most important calcium channels in [neurons](/entities/neurons) and cardiac myocytes. This channel plays critical roles in synaptic plasticity, gene transcription, and cellular excitability.

Function

Cav1.2 is an L-type voltage-gated calcium channel with several key characteristics:

• Channel Type: L-type calcium channel (Cav1.2)
• Primary Structure: Alpha-1 subunit with 4 repeat domains, each containing 6 transmembrane segments
• Biophysical Properties: High voltage activation, slow inactivation, dihydropyridine-sensitive
• Subcellular Localization: Somatodendritic compartment, [dendritic spines](/cell-types/dendritic-spines), cardiac cells

Key Roles in Neurons

Disease Associations

Timothy Syndrome (TS)

• Causative gene for Timothy syndrome, a multisystem disorder
• Gain-of-function missense mutations (e.g., G406R) cause prolonged channel opening
• Associated with cardiac arrhythmias, autism, seizures

Psychiatric Disorders

• Genome-wide significant association with bipolar disorder, schizophrenia, and major depressive disorder
• Risk SNPs in intronic regions affect gene expression and splicing
• May affect neuronal calcium signaling and synaptic plasticity

Alzheimer's Disease

• Altered Cav1.2 function affects calcium homeostasis in neurons
• Involved in [amyloid-beta](/proteins/amyloid-beta)-induced synaptic dysfunction
• Therapeutic target for calcium dysregulation in AD

Parkinson's Disease

• Cav1.2 channels regulate dopaminergic neuron function
• L-type channel blockers may protect dopaminergic neurons
• Altered expression in PD brain regions

Expression

• Brain: High expression in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), basal ganglia, cerebellum
• Heart: Cardiac muscle (ventricles, atria)
• Other Tissues: Smooth muscle, endocrine cells, fibroblasts

Therapeutic Targeting

• Dihydropyridines: Nimodipine, amlodipine ([blood-brain barrier](/entities/blood-brain-barrier) penetrant: nimodipine)
• Benzothiazepines: Diltiazem
• Phenylalkylamines: Verapamil
• Clinical Trials: L-type channel blockers being investigated for neuroprotection in AD and PD

Key Publications

Background

The study of Cacna1C Gene 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.

Molecular Mechanisms

Channel Structure

Cav1.2 channels are composed of:

• α1C subunit (CACNA1C): Forms the calcium-permeable pore
• β subunits (β1-β4): Modulate trafficking and gating
• α2δ subunits (α2δ1-4): Assist in channel assembly
• γ subunits: Tissue-specific modulators

Gating Properties

• Activation threshold: ∼-40 mV
• Activation kinetics: Relatively slow compared to other VGCCs
• Inactivation: Both voltage-dependent and calcium-dependent (CDI)
• Recovery: Slow recovery from inactivation

Calcium-Dependent Inactivation (CDI)

Cav1.2 channels undergo CDI, a unique feature:

• Calcium influx through the channel activates calmodulin
• Calmodulin binds to the C-terminal tail
• This triggers channel closure even during continued depolarization
• Protein kinase CK2 and CaMKII modulate CDI strength

Phosphorylation

PKA phosphorylation of Cav1.2:

• Increases channel open probability
• Enhances L-type current amplitude
• Critical for β-adrenergic regulation of cardiac function
• Dysregulation linked to neuropsychiatric disorders

Therapeutic Targeting

Clinical Applications

CNS Drug Development

• Isradipine: Under investigation for PD neuroprotection
• DKK1 inhibitors: Targeting Cav1.2 channel regulation
• Allosteric modulators: Preferring brain isoform

Animal Models

• CACNA1C knockout: Embryonic lethal (cardiac requirements)
• Conditional KO: Brain-specific deletion shows cognitive deficits
• Mutant mice: Timothy syndrome model shows autism-like behaviors

Research Directions

• Isoform-selective blockers for CNS disorders
• Gene therapy approaches for channelopathies
• Understanding isoform-specific functions in brain
• CACNA1A Gene - Related P/Q-type calcium channel
• [Calcium Channel Genes](/genes) - Gene family
• L-type Calcium Channel Blockers - Therapeutic class

External Links

• [NCBI Gene: CACNA1C](https://www.ncbi.nlm.nih.gov/gene/775)
• [UniProt: CACNA1C](https://www.uniprot.org/uniprot/Q13936)
• [Ensembl: CACNA1C](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000132938)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving CACNA1C Gene discovered through SciDEX knowledge graph analysis: