Voltage Gated Calcium Channel Assays
Background of Voltage Gated Calcium Channel
Voltage gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are important transducers of membrane potential changes into intracellular Ca2+ transients. In general, VGCCs are closed at physiologic or resting membrane potential, whereas can be activated at depolarized membrane potentials.
Physiological Functions of Voltage Gated Calcium Channel
The Ca2+ channels can regulate and induce various physiological events by controlling the concentration of intracellular Ca2+. Activation of VGCCs may lead to activation of calcium-sensitive potassium channels, muscle contraction, neuronal excitation, upregulation of gene expression, as well as the release of hormones or neurotransmitters. In summary, VGCCs are key signaling sensors of electrical excitability.
Fig.1. Signal transduction by voltage-gated Ca2+ channels. (Zamponi, 2005)
Types of Voltage Gated Calcium Channel
Since the first recording of Ca2+ currents in cardiomyocytes in 1979, there are 6 types of Ca2+ currents according to specific physiological and pharmacological properties. L-type Ca2+ currents have slow voltage-dependent inactivation and are regulated by second messenger-activated protein phosphorylation in multiple cell types. T-type Ca2+ current is negatively voltage-dependent and insensitive to conventional Ca2+ antagonist drugs available at the time. The remaining N-, P/Q- and R-type Ca2+ currents are most prominent in neurons.
| Type | α1 Subunits | Specific Blocker | Principal Physiological Functions | Inherited Diseases |
| L | Cav1.1 | DHPs | Excitation-contraction coupling in skeletal muscle, regulation of transcription. | Hypokalemic periodic paralysis |
| Cav1.2 | DHPs | Excitation-contraction coupling in cardiac and smooth muscle, endocrine secretion, neuronal Ca2+ transients in cell bodies and dendrites, regulation of enzyme activity, and regulation of transcription. | Timothy syndrome: cardiac arrhythmia with developmental abnormalities and autism spectrum disorders | |
| Cav1.3 | DHPs | Endocrine secretion, cardiac pacemaking, neuronal Ca2+ transients in cell bodies and dendrites, auditory transduction. | ||
| Cav1.4 | DHPs | Visual transduction | Stationary night blindness | |
| N | Cav2.1 | ω-CTx-GVIA | Neurotransmitter release, Dendritic Ca2+ transients | |
| P/Q | Cav2.2 | ω-Agatoxin | Neurotransmitter release, Dendritic Ca2+ transients | Familial hemiplegic migraine, cerebellar ataxia |
| R | Cav2.3 | SNX-482 | Neurotransmitter release, Dendritic Ca2+ transients | |
| T | Cav3.1 | None | Pacemaking and repetitive firing | |
| Cav3.2 | Pacemaking and repetitive firing | Absence seizures | ||
| Cav3.3 |
Assay List of Voltage Gated Calcium Channel
Creative Biolabs can provide a range of assays of voltage gated calcium channels. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Voltage-gated calcium channels: their discovery, function and importance as drug targets |
| Journal | Brain and neuroscience advances |
| Published | 2018 |
| Abstract | This article describes the importance of Ca2+ entry for excitable cell function and has identified multiple calcium conductance isoforms in different tissues. These are known as low- and high-voltage activation currents, and can be further subdivided into L-, N-, PQ-, R-, and T-type calcium currents, as well as single-channel conductance. In subsequent experiments, we further investigated the physiological and pathophysiological roles of calcium channels through knockout and other mutant mice. Cardiovascular L-type channels have been shown to be widely used targets of antihypertensive drugs and N-type channels are targets of analgesic drugs. Research in recent years has enabled a better understanding of Ca2+ penetration and the structure of the pore-forming and accessory subunits. In addition, voltage-gated calcium channels are affected by multiple regulatory pathways regulated by G proteins and second messengers. Further studies on trafficking pathways, subcellular localization, and functional specificity are required in the future. |
| Result |
Selective pharmacology, which is important to dissect the function of different calcium channels, remains incomplete. Selective inhibitors of the different CaV1 channels are not currently available. Although the omega-conotoxin GVIA is a selective blocker of N-type channels, the efficacy of small-molecule inhibitors of N-type channels in clinical trials for chronic pain remains to be verified. Future studies of how specific calcium channels are trafficked to precise subcellular domains are needed. Studies have shown that calcium channels can interact with various scaffold proteins, ion channels, and second messenger pathways. Subsequent studies need to focus on the mechanism by which they work. In addition, the signaling pathway of intracellular Ca2+ to the nucleus and the selectivity of L-type Ca2+ channels in neurons are also required.
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Fig.2. Single calcium channels with different properties, and topology of the channels. (Dolphin, 2018)
References
- Zamponi, G. Voltage-gated calcium channels. Eurekah. com and Kluwer Academic/Plenum Publishers. 2005.
- Dolphin, A.C. Voltage-gated calcium channels: their discovery, function and importance as drug targets. Brain and neuroscience advances. 2018, 2: 2398212818794805.
