Clc-2 Case Study

Contractility of ASM requires an increased levels of intracellular Ca2+. When surface receptors are not activated, Ca2+ levels are low. Upon activation of these cell surface receptors by contractile agonists e.g. acetylcholine, serotonin and histamine, intracellular Ca2+ increases causing a contraction (9). Smooth muscle cell contraction is controlled by both receptor and mechanical activation of proteins actin and myosin and also changes to membrane potential.

While completing CLDE 5160 I began to develop a deeper understanding of the history of bilingual education. For standard 5.a I have selected the completed case study as my artifact. The reason I selected my case study as the artifact for this standard was because we developed it over the course of the semester and now it shows my growth as an educator. I completed this artifact prior to starting my first year as a teacher of record on the school that I had been hired to teach at.

Agus ZS, Morad M. Modulation of cardiac ion channels by magnesium. Annu Rev Physiol 1991; 53:299.

Hyperkalemic Periodic Paralysis Disease (HYPP) is a muscular disorder found prominently in horses that occurs due to an inherited genetic mutation [1]. Specifically, a point mutation in the sodium channel gene, found in the muscle of affected horses, is passed on to offspring [1]. Sodium channels found in the muscle cell membrane primarily control muscle fiber contraction [1]. According to research summarized by UC Davis, when this defective sodium channel gene is present, the channels “leak” due to fluctuation of blood potassium levels, causing the muscle to depolarize and to contract involuntarily [4]. These fluctuating potassium levels may result from a period of fasting, followed by intake of high potassium feed, such as alfalfa [1]. Ultimately, the depolarization causes the muscles to lose their effectiveness, and myopathy eventually develops [4]. All horses positive for the HYPP gene mutation are affected for their entire lives [2].

Chloride channels are a structurally diverse superfamily of transmembrane proteins that facilitate the transport of negative anions across the cell membrane. These channels are involved in a plethora of physiological processes such as neurotransmission, excitation of skeletal, cardiac, and smooth muscle, salt transport, cell volume regulation, and acid production in internal and external compartments. Families of these channels include the voltage-gated CLC family, calcium-activated CaCC family, GABAA receptors, glycine receptors, and the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an ATP-binding cassette (ABC) transporter that is responsible for proper fluid transport across the epithelial membrane of various cells

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

In patients with CF, dysregulation of sodium and chloride ions transport may lead to multiple organ damage. Depending on the type of gene mutation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, the patient may have various clinical

What played the biggest role in my decision to apply to CMC was its large array of resources. From its top research institutions to the numerous amount of classes provided throughout the Claremont colleges, CMC provides its students with some of the best resources and opportunities that a undergraduate school has to offer. However, out of all the opportunities and resources that CMC could provide, I believe that the Athenaeum caught my attention the most.

Skeletal muscle contraction follows the sliding filament model. When an action potential is delivered to a muscle fiber, Ca2+ ions are released from the sarcoplasmic reticulum and diffused into the sarcoplasm. The Ca2+ ions bind to the troponin, exposing myosin-binding

Cystic fibrosis (CF) is the most commonly inherited, autosomal recessive disease in the UK with approximately 1 in 2500 people being affected (6). The disease stems from a mutation in the protein forming the Cystic Fibrosis transmembrane conductance regulator (CFTR), a chloride channel regulating the transport of ions across epithelial cell membranes. Dysfunctional CFTR channels are incapable to transporting chloride ions to the luminal surface and consequently water doesn’t follow osmotically. Coupled

Today is the beginning of our first CLC assignment. Collaboratively working together to accomplish this week’s task alongside the other CLC assignment weekly assignment going forward. The focus as a whole needs to factor: Making a point of contact, aligning individual’s strengths in areas to complete the assignments, and individual responsibilities. These assignments require weekly leadership, and a submitter. Please let’s text, or call one another today to get this ball on the roll. Looking forward to speaking and working with you all and together I believe we will succeed. I will initiate today’s point of contact to the team through text please feel free to call me any time after 3:45pm (Arizona time zone).

Excitation-contraction coupling (ECC) is the connection between the electrical action potential and the mechanical muscle contraction. Physiologically, it is a mechanism whereby an electrical signal detected by the dihydropyridine receptor is converted into an increase in calcium via activation of ryanodine receptors (RyRs). Per the article, mutations in RYR1, the gene encoding, are the underlying cause of various congenital myopathies including central core disease, multiminicore disease (MmD), which is a disorder that primarily affects muscles used for movement, as well as some forms of centronuclear myopathy (CNM), a condition characterized by muscle weakness, and congenital fibre-type disproportion. Patients with recessive, but not dominant,

High throughput screening of CaCCs can help us identify the specific activators and inhibitors of these channels and with the help of fully-controlled electrophysiological experiments combined with biochemical and biophysical studies, we can unravel therapeutic targets of CaCCs for the treatment of cystic fibrosis and other diseases related to chloride dysregulation. Though the discovery of ANO1 and ANO2 as CaCCs has revolutionized our understanding of the great role that anion’s homeostasis could play in different physiological and pathological conditions, there still are some important questions needed to be answered. In comparison to ANO1, ANO2 activation kinetics are faster 49, ANO2 has less sensitivity to Ca2+ concentrations 27 and provides smaller single unit conductance 90, issues that should be considered more seriously upon realizing why the existence of different ANO isoforms (ANO1 and ANO2) with diverse characteristics is necessary in the cells. It is still unknown if these discrete characteristics can be assigned to specific modules. In addition to other members of the Anoctamin family, other transmembrane proteins with ambiguous function should be studied to see if they have the same characteristics of CaCCs or other related channels and transporters responsible for the flow of Cl− and other anions across the biological membranes. As well, the regulatory roles that cations can play in regard

While contraction in skeletal muscle is triggered by motor neurons under central control, certain cardiac muscle variants exhibit autorhythmicity. This means that that they are capable of producing their own depolarizing electrical potential. The cardiomyocytes that are capable of producing their own electrical potentials are found in what is referred to as the electrical condition system of the heart. This system is comprised of specializes cardiomyocytes that are autorhythmic and are able to conduct electrical potentials rapidly. These specialized structures include the sinoatrial node, atrioventricular node and bundle, and Purkinje fibers.

The Na-K-Cl cotransporter is a group of ubiquitous membrane transport proteins. This secretory cotransporter maintains electroneutrality by transporting ions with the stoichiometry of 1Na+: 1K+: 2Cl-. Two different gene isoforms of the Na-K-Cl cotransporter have been found. Both varieties of the symporter act to regulate and maintain cell volume and intracellular Cl- concentrations. However, the two different isoforms of NKCC vary structurally as although NKCC2 is around 60% homologous to NKCC1, it is lacking exon 21 (Delpire et al., 1994). The loss of this exon leads to the differential sorting of the two isoforms therefore they are targeted to different membrane domains (Carmosino et al., 2008). The first isoform, NKCC1, is a major component in mediating Cl- influx in the basolateral membrane. Contrastingly, NKCC2 is selectively expressed in the apical membrane of cell such as in thick ascending limb of Henle and primarily involved in NaCl reabsorption (Darman and Forbush, 2002).