Introduction Epilepsy is a serious global problem that affects approximately 1% of people worldwide (1). Epilepsy is a chronic condition of the central nervous system (CNS) characterized by epileptic seizures, which can affect physical and mental functions (2). Epileptic seizures are unprovoked reoccurring episodes of abnormal, excessive, or hypersynchronis neuronal activity in the CNS (2). The treatment options of epilepsy include medications called antiepileptic drugs (AED) and surgeries based on individuals’ specific diagnosis and background (1). The AED Keppra®, S-enantiomer of α-ethyl-2-oxo-1-pyrrolidine acetamide, or Levetiracetam (LEV) is Food and Drug Administration (FDA)-approved for the treatment and prevention of epileptic …show more content…
The ability of HVA Ca2+ channels to alter the firing pattern of postsynaptic neurons makes regulation of HVA Ca2+ channels a means to help prevent hypersynchronis neuronal activity and prevent epileptic seizures. The synaptic vesicle protein 2A (SV2A) is a protein in neurons that is important for calcium-regulated secretion of neurotransmitters (6). The protein SV2A regulates neurotransmitter release by affecting the expression of the Ca2+ sensor protein synaptotagmin, by reducing Ca2+-mediated vesicle exocytosis and thereby reducing neurotransmitter release (6). The ability of SV2A to affect synaptotagmin expression and reduce exocytosis makes regulation of SV2A binding a means to prevent abnormal neuronal activity and prevent epileptic seizures. The ryanodine receptors (RyRs) are intracellular Ca2+ channels that are a cellular mediator for calcium-induced calcium release (CICR) (1). The inositol 1,4,5-triphosphate receptors (IP3R) are intracellular Ca2+ channels that act as a cellular mediator for CICR through their activation of a second messenger that causes the release of Ca2+ (1). In the process of CICR Ca2+ is released from intracellular storage (3). In the development of epilepsy, a dysregulation of intracellular calcium ([Ca2+] i) by inositol 1,4,5-triphosphate receptors (IP3R) and ryanodine receptors (RyR)
At the molecular level of explanation these processes are dependent on the interplay between glutamate receptors, Ca2+ channels, the increase of intracellular Ca2+ levels, Ca2+-dependent proteins like Akt, ERK, mTOR and neurotrophins such as brain derived neurotrophic factor (BDNF) (24, 25).
Rascati KL; Richards KM; Johnsrud MT; Mann TA. (2009). Effects of antiepileptic drug substitutions on epileptic events requiring acute care. pharmacotherapy.
Calcium needs to be released first and needs to be obtained in the body in order for the body to carry out its function. Calcium or calcium ion (Ca2+) is stored in the sacroplasmic reticulum (SR) to start contraction for the muscles.11 In the case of the cardiac muscle, it would start contraction through the Sodium-Calcium exchange (NCX) and with limited help of the SR. Sodium ions (Na+) would enter from the dyadic cleft, the space where the cell membrane and SR are in close proximity.11 This would cause Ca2+ to flow out of the cell. In order for Ca2+ to reenter it has to go through Ca2+ channels and so Ca2+ would be released.11 Excitation-contraction coupling relies on the dyadic cleft of Ca2+ to be released. Understanding how NCX works could help provide treatment for HF because the cardiac muscle could be manipulated to contract. It may be possible to remove the NCX because it can cause too much Ca2+ to be stored in the SR and cause arrhythmias and cell death.11 This would lead to a pathway to fixing any heart failure
Epilepsy affects about 65 million people around the world. In average, the incidence of epilepsy is about 150,000 people every year in the United Stated (Schachter, Shafer, and Sirven, 2013). It is a neurological disease of the brain marked by recurrent unprovoked seizures. Likewise, the recurrent unprovoked seizures are temporary disturbances of the brain function due to abnormal, excessive electrical activity in the brain (“Fact,” n.d.). Seizures may vary from person to person, thus, they are sub-classified into different types of seizures. They reoccur at unexpected times, so this has led to several different innovations to aid people with seizures to alert and to prevent the risks of seizures. In this paper, the information and importance
The most frequent inflammatory disease of the central nervous system (CNS) impacts the lives of two and half million people in the world, Multiple Sclerosis (MS) (Schattling, 2013). Growing up, this disease has personally affected my family, and seeing a first hand account of the burden and turmoil that this disease causes for all of its patients it is critical to understand how this disease degenerates neurons and axons. The key players in this process are nervous system ion channels that regulate the influx and efflux of sodium and calcium, whether through exchangers or voltage-gated channels. There are normal molecular settings in neurons and there are MS molecular settings; the two are very different and progressively become further
As stated by (Muscles, 2015) “If a muscle cell fires an action potential, which is as a result of the motor neuron command. Then it causes the release of calcium ions, which are released from the sarcoplasmic reticulum” Sarcoplasmic reticulum is a specialised type of smooth ER that regulates the calcium ion concentration in the cytoplasm of striated muscle cells (Sarcoplasmic Reticulum Cell Biology, 2015).
NMDA Receptor is one of the crucial glutamate receptors present in the nerve cell. It gets activated when glutamate or Glycine binds to it. NMDA receptor is known for its role in synaptic plasticity and membrane function (learning and memory). Its activity is highly dependent on calcium influx. It is a tri heteromeric receptor with three different subunits NR1, NR2 and NR3. Each subunit has several other subunits, each of them having a unique function: NR1 has 8, NR2 has 4 (NR2A, NR2B, NR2C, NR2D), NR3 has 2 (NR3A, NR3B). Out of all the subunits, NR2A and NR2B have been extensively studied. NR2A, also known as GluN2A is believed to be involved in cell death pathways whereas NR2B, also known as GluN2B is believed to be involved in cell survival cascades (Bayer et al., 2006). Interestingly, GluN2B and GluN2A have differing roles, and both can affect either long-term potentiation (LTP) or long-term differentiation (LTD)
‘Epilepsy’ comes from the ancient Greek word which means epilepsia, meaning seizure. According to Epilepsy Foundation of Eastern Pennsylvania, “Epilepsy is a brain disorder that causes seizures, which is a change in the normal brain actively.” Seizures which is not a disease resulting from unusual electrical activity in the brain is a significant symptom for epilepsy. Epilepsy seizures last from few seconds to couple of minutes. While all seizures are not related with epilepsy, generalized seizure, Focal seizure, Status epilepticus are significant seizures for epilepsy. Epileptic seizures are formed by abnormal electricity producing from the brain. There are several kinds of epilepsy with different types of seizures. There is no specific age group, race, nationality or social level who are suffers most in epilepsy. People from all ages can affected by epilepsy, specially from two to sixty-five ages are more affected. It is very important for neurologist to early diagnose the type of epilepsy. Patient having multiple epilepsy with variety of seizures, without early diagnosis all of them it is very tough to treatment a patient in an effective way.
Starting from the top with Group I ACs, this includes ACs 1, 3, and 8, this group is stimulated by the Ca2+/calmodulin signaling pathway via direct binding of calmodulin (CAM) to the ACs.9 A majority of the evidence of stimulation comes from overexpression system studies, but current evidence on the mechanism by which the binding of CAM to AC1, 3, or 8 stimulates activity has yet to be deciphered in a cohesive manner.9 However, on the other end of the spectrum exists Group III ACs, which includes ACs 5 and 6. The Ca2+/CAM signaling pathway inhibits their activity. Structural analyses done on ACs 5 and 6 provide evidence indicating that the Ca2+ ion displaces Mg2+ ions in the active site.10 Figure 3 shows the active site with emphasis on the Asp396 and Asp440, but also shown is their interactions between a Mn2+ ion and a Mg2+ ion. The
Glutamate receptors (NMDAR and AMPAR) of the postsynaptic membrane are the initial triggers for LTP induction. NMDARs require the binding of glutamate and the co-agonist glycine, as well as depolarization of the postsynaptic membrane, to become activated and permeate Na+, K+ and Ca2+. Most of AMPARs contain GluA2 and permeate Na+ and K+. Glutamate binding to the AMPARs causes a Na+ influx into the postsynaptic neuron. This depolarization leads to Mg2+ block releasing from NMDARs. Glutamate binding and the Mg2+ removal opens NMDARs, Ca2+ and Na+ then flow into the postsynaptic neuron. Through repeated activation of the postsynaptic neuron, sufficient Ca2+ comes in and triggers a series of molecular events required for LTP
c. Ca2+ dependent protease, calpains, is a key player and responsible in the degeneration of the axon and synapse during Wallerian degeneration (Ma, M., Ferguson, T. A., Schoch, K. M., Li, J., Qian, Y., Shofer, F. S., . . . Neumar, R. W., 2013).
In order for an axon to send information, it has to release neurotransmitter stored in the synaptic vesicles in the axon terminal. In order for this to occur, Ca2+ ions must first be present in the axon terminal, and an action potential must have been initiated. This experiment will be researching if Ca2+ levels in an extracellular solution will affect the amount of neurotransmitter released at an axon terminal. Will a larger concentration of Ca2+ ions present in the extracellular fluid, induce a greater release of neurotransmitter, and if there is no Ca2+ present in the solution, will no neurotransmitter be released?
Overstimulation or prolonged activation of excitatory amino acid receptors is called excitotoxicity (64, 65). Overactivation of these excitatory receptors causes opening of post-synaptic ion channels which consequently increases intracellular Ca2+ and this affects Ca2+ regulatory mechanisms. Excitotoxicity seems to be a major contributor to many neurodegenerative disorders such as PD, AD and HD (65, 66). Although the pivotal role of excitotoxicity in neurodegenerative disorders has been proved, the exact mechanisms through which it promotes neurodegeneration still is unclear and more studies are needed (67). The N-methyl-D-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate (AMPA) subtypes are the main determinants,
Although there is no cure for epilepsy, there are many different drug treatments can be effective in prevention seizures, including benzodiazepines or barbiturates. However, breakthrough seizures are still possible.1 Due to the unpredictable nature of seizures, epileptic patients often experience a lower quality of life since they cannot drive and cannot work in certain job fields. Furthermore, seizures can also lead to many different types of injuries in epileptic patients, some of which could be fatal, such as choking on the tongue. In the United States alone one in twenty-five people suffer from epilepsy.2
Epilepsy is a condition in which a person has two or more seizures affecting a variety of mental and physical functions. Epilepsy is one of the oldest conditions of the human race. Epilepsy Awareness is important because Epilepsy is a widely misunderstood disorder. The reason that Epilepsy has been misunderstood has been mainly due to research not being conducted until the middle of the nineteenth century. There are six main types of seizures and many treatments that can assist an epileptic patient. Many facts and myths exist about a person who has Epilepsy, which, is why it is an important disorder to understand. A person living with Epilepsy can typically have a normal life after seeking medical advice from doctors.