Involvement of Voltage-Gated Calcium Channels in Inflammation and Inflammatory Pain
Fumiko Sekiguchi1, Maho Tsubota1, Atsufumi Kawabata1
1Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University.
Insights
Voltage-gated calcium channels (VGCCs) are implicated in inflammatory pain. The Cav3.2 T-type VGCC shows promise as a therapeutic target for visceral inflammatory pain conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Voltage-gated calcium channels (VGCCs) are crucial for neuronal function.
- High-voltage-activated (HVA) channels and T-type (Cav3.1-3.3) channels represent distinct VGCC classes.
- Gabapentinoids, targeting HVA α2δ subunits, are effective in neuropathic and inflammatory pain.
Purpose of the Study:
- To investigate the role of Cav3.2 T-type VGCC in visceral inflammation and pain.
- To explore Cav3.2 as a potential therapeutic target for inflammatory pain disorders.
Main Methods:
- Review of existing literature on VGCCs, inflammatory mediators, and pain pathways.
- Analysis of Cav3.2 expression and function in primary afferents.
- Examination of inflammatory mediator modulation of Cav3.2 activity.
Main Results:
- Cav3.2 is highly expressed in primary afferents, influencing neuronal excitability and neurotransmitter release.
- Inflammatory mediators like hydrogen sulfide (H2S) modulate Cav3.2 activity.
- Increased Cav3.2 activity by H2S is linked to colonic, bladder, and pancreatic pain and visceral inflammation.
Conclusions:
- VGCCs, particularly Cav3.2 T-type channels, play a significant role in inflammation and inflammatory pain.
- Cav3.2 represents a promising therapeutic target for visceral inflammatory pain conditions such as IBS, IC/BPS, and pancreatitis.
Abstract:
Voltage-gated calcium channels (VGCCs) are classified into high-voltage-activated (HVA) channels and low-voltage-activated channels consisting of Cav3.1-3.3, known as T ("transient")-type VGCC. There is evidence that certain types of HVA channels are involved in neurogenic inflammation and inflammatory pain, in agreement with reports indicating the therapeutic effectiveness of gabapentinoids, ligands for the α2δ subunit of HVA, in treating not only neuropathic, but also inflammatory, pain. Among the Cav3 family members, Cav3.2 is abundantly expressed in the primary afferents, regulating both neuronal excitability at the peripheral terminals and spontaneous neurotransmitter release at the spinal terminals. The function and expression of Cav3.2 are modulated by a variety of inflammatory mediators including prostanoids and hydrogen sulfide (H2S), a gasotransmitter. The increased activity of Cav3.2 by H2S participates in colonic, bladder and pancreatic pain, and regulates visceral inflammation. Together, VGCCs are involved in inflammation and inflammatory pain, and Cav3.2 T-type VGCC is especially a promising therapeutic target for the treatment of visceral inflammatory pain in patients with irritable bowel syndrome, interstitial cystitis/bladder pain syndrome, pancreatitis, etc., in addition to neuropathic pain.
More Related Videos
06:54Author Spotlight: Enhanced Method for Evaluating Analgesic Effects — Dual Hind Paw Carrageenan Injection in Mice
Published on: November 15, 2024
11:42Reconstitution of a Transmembrane Protein, the Voltage-gated Ion Channel, KvAP, into Giant Unilamellar Vesicles for Microscopy and Patch Clamp Studies
Published on: January 22, 2015
Related Concept Videos
Voltage-gated Ion Channels
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Non-gated Ion Channels
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
Mechanically-gated Ion Channels
Ligand-gated Ion Channels
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...
G-Protein Gated Ion Channels
Sensory...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
