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Neuro–Endocrine–Immune Dysfunction in the Chronic Pain Patient
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
The increased intracellular concentration of Ca2+ promotes the externalization of phospholipases to the cell membrane which then cleave arachidonic acid and is acted upon by cyclooxygenase to produce prostanoids. Prostaglandins act pre- and post-synaptically. The pre-synaptic effect enhances the opening of voltage gated calcium channels. Post-synaptically, glycine receptors are inhibited. Glycine typically acts as an inhibitory neurotransmitter on the second-order neuron.
Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
The span of presynaptic membrane that contains the primed vesicles and the dense collection of SNARE proteins is referred to as the active zone. Voltage-gated calcium channels are highly concentrated around the active zones and open in response to membrane depolarization at the synapse. The influx of calcium is sensed by synaptotagmin 1, which in turn dislodges the complexin protein and allows the vesicle to fuse with the presynaptic membrane and release the neurotransmitter. It has also been shown that the voltage-gated calcium channels directly interact with the t-SNAREs syntaxin 1A and SNAP-25, as well as with synaptotagmin 1. During exocytosis, v-SNAREs (e, g., synaptobrevin) and t-SNAREs (e.g., syntaxin and SNAP-25) assemble into a core trans-SNARE complex. This complex plays multiple roles during the various stages of exocytosis, including priming, fusion, pore formation, and expansion, eventually resulting in the release of the vesicle content.
Mitochondrial Dysfunction and Heart Diseases
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
There are two types of voltage-gated calcium channels: the L- (low threshold) and T- (transient) type channels. The L-type Ca2+ channel (LTCC) is predominantly in ventricular cardiomyocytes, while the T-type Ca2+ channel is mainly in pacemaker and conduction systems.116 ROS has been shown to have various effects on LTCC, although whether ROS increase or decrease L-type Ca2+ channel current (ICaL) in cardiomyocytes remain controversial, depending on the experimental models.
Current and promising therapeutic options for Dravet syndrome
Published in Expert Opinion on Pharmacotherapy, 2022
Antonella Riva, Gianluca D’Onofrio, Elisabetta Amadori, Domenico Tripodi, Ganna Balagura, Valentina Iurilli, Maria Stella Vari, Alberto Verrotti, Pasquale Striano
Another drug repurposed for its possible anti-seizure effect is verapamil, a voltage-gated calcium channel blocker that can offer interesting results [53,54]. Nevertheless, current evidence is set at small case series and sporadic cases description. Starting from 2009, Iannetti et al. [55] described the case of two girls with DS treated with add-on verapamil from a starting dose of 1 mg/kg/day up to a target dose of 1.5 mg/kg/day. Both girls experienced a prompt response in controlling SE, myoclonic jerks, and focal onset and primarily generalized seizures, although in one girl, the therapeutic effect blurred after 13 months of treatment. No AE, except for a slight subclinical increase of phenytoin plasma levels, was observed during treatment. Later, Nicita and colleagues [56] enrolled 7 patients with DRE of different aetiologies (including 4 patients with DS) to be treated with add-on verapamil up to 14 months. Results directly pointed toward better seizure control for those patients with genetically determined DS, but once again all seizure types were well controlled for a maximum of 13 months. No AEs were reported. Hence, further observational studies will be needed to dissect the real efficacy of this calcium channel blocker over epileptic channelopathies.
Cellular Calcium Signals in Cancer Chemoprevention and Chemotherapy by Phytochemicals
Published in Nutrition and Cancer, 2022
Xue Li, Shuhan Miao, Feng Li, Fen Ye, Guang Yue, Rongzhu Lu, Haijun Shen, Yang Ye
Voltage-gated calcium channels (VGCCs) are composed of α, β, γ and δ subunits and have five subtypes, the L-type, N-type, T-type, R-type and P/Q-type, depending on the α1 subunit genes (40, 41). VGCCs are mainly expressed on the membrane of excitable cells such as neurological cells and brain cells regulating cell electrical signals by extracellular Ca2+ influx (42). Cytosolic Ca2+ exported by VGCCs regulates a wide variety of physiological and pathophysiological processes including cell proliferation, apoptosis, migration and cell death (43). The different level and types of VGCCs may cause unequal effects in cancers such as proliferation, metastasis and invasion. A meta-analysis demonstrated that some VGCCs are expressed at low levels in tumor tissues compared with expression in normal tissues, which as tumor suppressor in specific types of cancers (44). In contrast, some VGCCs subunits are over-expressed in cancers and promote cancer development. In invasive lobular breast cancer, the expression of CACNA1C, an L-type calcium channel subunit of VGCCs, increased cell metastasis ability (45), and the level of P/Q type VGCC antibodies was elevated in 16 of 39 (41%) patients with paraneoplastic cerebellar degeneration (46). Hence, targeting VGCC subunits in specific types of cancer may be a novel method for cancer treatment.
Neurological effects of static and extremely-low frequency electromagnetic fields
Published in Electromagnetic Biology and Medicine, 2022
A comprehensive study (Chung et al. 2015) demonstrated that ELF MF exposure affected the levels of different transmitters and their metabolites in the rat brain including: norepinephrine, serotonin, dopamine, glutamine and nitric oxide. Interestingly, changes varied with the brain regions studied (cortex, cerebellum, hippocampus, striatum and thalamus). Related to this is that Cichoń et al. (2017) reported an increase in nitric oxide metabolites, suggesting an increase in nitric oxide activity in the brain, with a concomitant improvement in functional and mental status in post-stroke patients exposed to ELF EMF. Activation of voltage-gated calcium channels controls the activity of nitric oxide synthase, the enzyme involved in nitric oxide synthesis. Involvement of voltage-gated calcium channels in the biological effects of EMF is a hotly debated topic recently (Pall 2013). However, calcium plays important roles in neural activities and functions. It is very possible that voltage-gated calcium channels are involved in the effects of static/ELF EMF on the brain, an electrical body organ.