Defective Ca2+ channel clustering in axon terminals

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This article discuss a defectives in calcium channels clustering in axon terminals that disturbs excitability in motoneurons resulting in spinal muscular atrophy. The article defines Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. SMA is essential the death of motor neurons. This disease is more common in children. This disease is process and will result in immobilization of individual who have it. The article discuss two specific genes that are associated with this disease, they are SMN1 and SMN2.

The SMN1 gene is responsible to determine the length of a protein. The SMN2 gene code for a truncated protein lacking the functionally important domains at the C terminus that are encoded by exon 7(defined by the article). SMA is caused due to lack of SMN1, causing the lack of axon elongation. In the study they noticed that mice lose most of their motoneuron abilities during the critical development period. This means that when some is born they have full motoneuron capabilities. Within the time period after birth were these motoneuron issues begin was a major focus of this experiment. They article concluded that these motoneuron problems in SMA patients are a result of differentiation of motor endplates.

This article also focus its experiment on Cyclic adenosine monophosphate (cAMP). cAMP is defined as a cyclic nucleotide, adenosine 3′,5′-cyclic monophosphate, that serves as an intracellular, and sometimes extracellular, “second messenger” mediating the action of many peptide or amine hormones. Basically means that they help to get certain hormones inside the cell; hormones like epinephrine, which that otherwise could not do the intended response or reaction. Its main purpose is of cAMP is to activate of protein kinases. Protein kinase can then modify other proteins by adding phosphate group to them commonly known as phosphorylation. The article concluded that 8-CPT cAMP enhances spontaneous Ca2+ influx into spinal motoneuronsm. Which means that this specific 8-CPT cAMP might be a possible treatment for SMA patients.

Overall, I found this article to be extremely interesting and really content rich. I think this study might give individuals suffering from SMA some hope for future research that might lead to a possible treatment. Also I was surprised that calcium plays such a huge role in disease like SMA. I definitely recommend this article 

Seeing is believing! Imaging Ca2+-signalling events in living cells.

A.) activation of Ca2+-activated K+ channels by Ca2+ sparks results in spontaneous transient outward currents (STOCs), hyperpolarizing the plasma membrane (increased membrane potential; Vm). This reduces activation of voltage-operated Ca2+ channels (VOCCs), decreasing Ca2+ influx and global [Ca2+]. This can act as a negative feedback mechanism, whereby localized Ca2+ release from the sarcoplasmic reticulum (SR) lowers mean cytosolic [Ca2+], restricting further store loading.

B.) spark-dependent activation of Ca2+-activated Cl− channels causes spontaneous transient inward currents (STICs), with membrane depolarization and Ca2+ channel activation. This results in positive feedback, with Ca2+ release from the SR promoting further Ca2+ influx.

Above is an image directly from the article.

The article discusses a study that take a closer look at what is happening with calcium on a cellular level. Some of this study is conducted on jellyfish. They used jellyfish because they were able to stain its protein with a fluorescent dye. The purpose of staining the proteins is to use them as bio-markers for a better understand of where the calcium is going and why. In their research was done because they know that muscle contractions require the presence of calcium. With the knowledge that calcium is required they then realized that calcium play a vital role in excitation of contraction coupling.Excitation of contraction coupling is defined  to describe the physiological process of converting an electrical stimulus to a mechanical response.This coupling is vital to muscle physiology.This article also calcium sparks which is depicted and explained above. Basically these Calcium sparks  act as the building blocks for larger transients during the contraction of cardiac muscle (at least in this study). These calcium sparks result in both inhibitory and excitatory responses. They do this by increasing and decrease calcium sensitivity. The calcium sparks are also responsible for both positive and negative feedback. Overall, this article was pretty difficult to navigate through, but it is definitely full of great proven research. The article conclude that they would like to conduct another experiment were they could take a closer look at the use of genetically coded calcium indicators expressed in organelle and/or tissue in identify specific purposes.  

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Calcium equilibrium in muscle.

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This article discusses a study conducted on frogs that compare the effect of calcium on muscle. Within the experiment they focused on 6 muscles of the frogs the tibialis anticus longus, peroneus, ileofibularis, sartorius, and the semitendinosus.The experiment itself was pretty complicated, they had each muscle dissected and soaked in 100 ml of solution. The solution consisted of  CaCls, NaC1, and KC1.The muscles were soaked for 5 hours and then tested to see the influx of calcium within a given muscle.

The reason for this experiment was to determine the permeability (ability to let things in or out of the cell)
of the muscle cell membrane to calcium.Also the experiments goal to calculate the energy requirements
to maintain the calcium in a steady state. This is vital to muscle metabolism because active working muscle needs calcium. This test will hopefully give us a ball park figure of are calcium influx within a given muscle.

Within this experiment they focused a huge part of the study on the metabolism satorius muscle of frogs. The flux of calcium within the cell during steady state was 0.8 mM/(liter hr) This information help to conclude the idea that their is a calcium pump within the muscle. The calcium pump is responsible for pushing calcium out of cell. The calcium that is being pump out of the cell must be coming out with quite some force, because going against a an chemical gradient.The flux is low but the maximum energy required per hour to pump calcium out of the cell against this high gradient is key in muscle metabolism.

Overall, I think this article does a great job on highlighting the need for calcium in muscle metabolism. I think its interesting to learn that their is in fact a mechanism within a given muscle that is responsible for the maintenance of calcium levels. Also i think it would be interesting to fin out how this mechanism to maintain calcium levels works in human muscle. 

How a muscle contraction is signalled - Animation

This Video is amazing it really grasps the main reason as to why calcium is so essential in the contration of any muscle. I hope you enjoy the video and can see a visual image of what is actually happening during a muscle contration on a mirco level :)

I choose this picture because it shows the daily recommendation of calcium for all different phase throughout life. Check it out and see if you close to your daily recommendation.