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A seizure is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with loss of consciousness, to shaking movements involving only part of the body with variable levels of consciousness, to a subtle momentary loss of awareness. These episodes usually last less than two minutes and it takes some time to return to normal. Loss of bladder control may occur.
Serine is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, a carboxyl group, and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC.
The N-methyl-D-aspartatereceptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and kainate receptors. Depending on its subunit composition, its ligands are glutamate and glycine (or D-serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Mg2+ ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a "coincidence detector" and only once both of these conditions are met, the channel opens and it allows positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions.
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium channels are regulated by the binding of a ligand. Other calcium channels can also be regulated by both voltage and ligands to provide precise control over ion flow. Some cation channels allow calcium as well as other cations to pass through the membrane.
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels.
Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy. It is defined as the sudden and unexpected, non-traumatic and non-drowning death of a person with epilepsy, without a toxicological or anatomical cause of death detected during the post-mortem examination.
Sodium channel protein type 5 subunit alpha, also known as NaV1.5 is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. NaV1.5 is found primarily in cardiac muscle, where it mediates the fast influx of Na+-ions (INa) across the cell membrane, resulting in the fast depolarization phase of the cardiac action potential. As such, it plays a major role in impulse propagation through the heart. A vast number of cardiac diseases is associated with mutations in NaV1.5 (see paragraph genetics). SCN5A is the gene that encodes the cardiac sodium channel NaV1.5.
N-type calcium channels also called Cav2.2 channels are voltage gated calcium channels that are localized primarily on the nerve terminals and dendrites as well as neuroendocrine cells. The calcium N-channel consists of several subunits: the primary subunit α1B and the auxiliary subunits α2δ and β. The α1B subunit forms the pore through which the calcium enters and helps to determine most of the channel's properties. These channels play an important role in the neurotransmission during development. In the adult nervous system, N-type calcium channels are critically involved in the release of neurotransmitters, and in pain pathways. N-type calcium channels are the target of ziconotide, the drug prescribed to relieve intractable cancer pain. There are many known N-type calcium channel blockers that function to inhibit channel activity, although the most notable blockers are ω-conotoxins.
Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.
Glutamate [NMDA] receptor subunit epsilon-1 is a protein that in humans is encoded by the GRIN2A gene. With 1464 amino acids, the canonical GluN2A subunit isoform is large. GluN2A-short isoforms specific to primates can be produced by alternative splicing and contain 1281 amino acids.
Sodium channel protein type 1 subunit alpha (SCN1A), is a protein which in humans is encoded by the SCN1A gene.
ATP-sensitive inward rectifier potassium channel 10 is a protein that in humans is encoded by the KCNJ10 gene.
Voltage-dependent calcium channel gamma-3 subunit is a protein that in humans is encoded by the CACNG3 gene.
Annette Catherine Dolphin is a Professor of Pharmacology in the Department of Neuroscience, Physiology and Pharmacology at University College London (UCL).
Chloride channel openers refer to a specific category of drugs designed to modulate chloride channels in the human body. Chloride channels are anion-selective channels which are involved in a wide variety of physiological functions and processes such as the regulation of neuroexcitation, transepithelial salt transport, and smooth muscle contraction. Due to their distribution throughout the body, diversity, functionality, and associated pathology, chloride channels represent an ideal target for the development of channel modulating drugs such as chloride channel openers.
Dimitri Michael Kullmann is a professor of neurology at the UCL Institute of Neurology, University College London (UCL), and leads the synaptopathies initiative funded by the Wellcome Trust. Kullmann is a member of the Queen Square Institute of Neurology Department of Clinical and Experimental Epilepsy and a consultant neurologist at the National Hospital for Neurology and Neurosurgery.
The Department of Pharmacology at the University College London, the first of its kind in England, was founded in 1905 and remained in existence until 2007.
Diane Lipscombe is a British neuroscientist who is a professor of neuroscience and the Reliance Dhirubhai Ambani Director of Brown University’s Robert J. and Nancy D. Carney Institute for Brain Science. She served as the president of the Society for Neuroscience in 2019, the world’s largest organization for the study of the brain and nervous system.
Willardiine (correctly spelled with two successive i's) or (S)-1-(2-amino-2-carboxyethyl)pyrimidine-2,4-dione is a chemical compound that occurs naturally in the seeds of Mariosousa willardiana and Acacia sensu lato. The seedlings of these plants contain enzymes capable of complex chemical substitutions that result in the formation of free amino acids (See:#Synthesis). Willardiine is frequently studied for its function in higher level plants. Additionally, many derivates of willardiine are researched for their potential in pharmaceutical development. Willardiine was first discovered in 1959 by R. Gmelin, when he isolated several free, non-protein amino acids from Acacia willardiana (another name for Mariosousa willardiana) when he was studying how these families of plants synthesize uracilyalanines. A related compound, Isowillardiine, was concurrently isolated by a different group, and it was discovered that the two compounds had different structural and functional properties. Subsequent research on willardiine has focused on the functional significance of different substitutions at the nitrogen group and the development of analogs of willardiine with different pharmacokinetic properties. In general, Willardiine is the one of the first compounds studied in which slight changes to molecular structure result in compounds with significantly different pharmacokinetic properties.
Raymond J Dingledine is an American pharmacologist and neurobiologist who has made considerable contributions to the field of epilepsy. He serves as Professor in the School of Medicine at Emory University, Atlanta GA, where he chaired the pharmacology department for 25 years and served as Executive Associate Dean of Research for 10 years.
References
- 1 2 UCL (2021-07-12). "Prof Stephanie Schorge". UCL Division of Biosciences. Retrieved 2022-01-06.
- ↑ "ORCID". orcid.org. Retrieved 2022-01-06.
- ↑ Admin, ERUK (2019-05-09). "Stephanie Schorge | Epilepsy Research UK". epilepsyresearch.org.uk. Retrieved 2022-01-06.
- 1 2 "Iris View Profile". iris.ucl.ac.uk. Retrieved 2021-12-30.
- ↑ "Royal Society announces prestigious University Research Fellowships for 2010 | Royal Society". royalsociety.org. Retrieved 2023-04-09.
- ↑ Schorge, S.; Gupta, S.; Lin, Z.; McEnery, M. W.; Lipscombe, D. (1999-09-02). "Calcium channel activation stabilizes a neuronal calcium channel mRNA". Nature Neuroscience. 2 (9): 785–790. doi:10.1038/12153. ISSN 1097-6256. PMID 10461216. S2CID 11155519.
- ↑ Lin, Z.; Lin, Y.; Schorge, S.; Pan, J. Q.; Beierlein, M.; Lipscombe, D. (1999-07-01). "Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons". The Journal of Neuroscience. 19 (13): 5322–5331. doi:10.1523/JNEUROSCI.19-13-05322.1999. ISSN 0270-6474. PMC 6782300 . PMID 10377343.
- ↑ Schorge, Stephanie; Elenes, Sergio; Colquhoun, David (2005-12-01). "Maximum likelihood fitting of single channel NMDA activity with a mechanism composed of independent dimers of subunits". The Journal of Physiology. 569 (Pt 2): 395–418. doi:10.1113/jphysiol.2005.095349. ISSN 0022-3751. PMC 1464248 . PMID 16223763.
- ↑ Schorge, Stephanie; Elenes, Sergio; Colquhoun, David (2005). "Maximum likelihood fitting of single channel NMDA activity with a mechanism composed of independent dimers of subunits". The Journal of Physiology. 569 (2): 395–418. doi:10.1113/jphysiol.2005.095349. ISSN 1469-7793. PMC 1464248 . PMID 16223763.
- ↑ Schorge, Stephanie (2018-02-14). "Channelopathies go above and beyond the channels" (PDF). Neuropharmacology. 132: 1–2. doi:10.1016/j.neuropharm.2018.02.011. ISSN 1873-7064. PMID 29454019. S2CID 3518363.
- ↑ Tate, Sarah K.; Depondt, Chantal; Sisodiya, Sanjay M.; Cavalleri, Gianpiero L.; Schorge, Stephanie; Soranzo, Nicole; Thom, Maria; Sen, Arjune; Shorvon, Simon D.; Sander, Josemir W.; Wood, Nicholas W. (2005-04-12). "Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin". Proceedings of the National Academy of Sciences of the United States of America. 102 (15): 5507–5512. Bibcode:2005PNAS..102.5507T. doi: 10.1073/pnas.0407346102 . ISSN 0027-8424. PMC 556232 . PMID 15805193.
- ↑ Wykes, Robert C.; Heeroma, Joost H.; Mantoan, Laura; Zheng, Kaiyu; MacDonald, Douglas C.; Deisseroth, Karl; Hashemi, Kevan S.; Walker, Matthew C.; Schorge, Stephanie; Kullmann, Dimitri M. (2012-11-21). "Optogenetic and Potassium Channel Gene Therapy in a Rodent Model of Focal Neocortical Epilepsy". Science Translational Medicine. 4 (161): 161ra152. doi:10.1126/scitranslmed.3004190. PMC 3605784 . PMID 23147003.
