Sandbox WWC6: Difference between revisions
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Hemolysins are most commonly proteins found in red blood cells that selectively allow for the diffusion of potassium ions across the membrane. <ref >https://en.wikipedia.org/wiki/Hemolysin#cite_note-pmid20692229-3</ref> or lipid biosurfactants that disrupt membrane composition resulting in cell lysis. These proteins are important for some erythrocyte nutrient accession, but cause massive erythrocyte destruction in bacterial infection, specifically responsible forhemolytic anemia, which causes fatigue, pain, arrythmias, and even heart failure in affected individuals.<ref>http://www.nhlbi.nih.gov/health/health-topics/topics/ha/</ref> Each hemolysin pore is composed of three subunits: the alpha subunit, which is the transmembrane ion channel, and two beta subunits that modulate channel gating and regulate the channel expression in the membrane. <ref name ="beta">PMID: 11486343</ref> <ref name = "sod"/> The alpha subunit is able to function independently of the beta subunit. <ref name = "beta"/> | |||
Hemolysins act through disruption of the cell membrane. Two main functions destroy phospholipid membranes: pore formation and phosphilipid hydrosysis. <ref>http://www.sciencedirect.com/science/article/pii/S0005273610002610</ref> Pore formation, the most common mechanism of hemolysin cell <ref name ="sod"/> This information was first discovered by Hodgkin and Huxley in 1952. <ref name ="physio">https://en.wikipedia.org/wiki/Hodgkin%E2%80%93Huxley_model</ref> For more information on the role of sodium channels in electrical signaling, click [https://en.wikipedia.org/wiki/Action_potential here]. | Hemolysins act through disruption of the cell membrane. Two main functions destroy phospholipid membranes: pore formation and phosphilipid hydrosysis. <ref>http://www.sciencedirect.com/science/article/pii/S0005273610002610</ref> Pore formation, the most common mechanism of hemolysin cell <ref name ="sod"/> This information was first discovered by Hodgkin and Huxley in 1952. <ref name ="physio">https://en.wikipedia.org/wiki/Hodgkin%E2%80%93Huxley_model</ref> For more information on the role of sodium channels in electrical signaling, click [https://en.wikipedia.org/wiki/Action_potential here]. | ||
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<scene name='69/696302/Beta-hemolysin/1'>Gamma-hemolysin</scene> | <scene name='69/696302/Beta-hemolysin/1'>Gamma-hemolysin</scene> | ||
==Pathogenic Microorganisms== | |||
Pore-forming toxins have been shown to closely relate to the pathogenicity of the toxin-producing organism <ref>http://www.ncbi.nlm.nih.gov/pubmed/1930675<ref> | |||
[[Image:640px-Sodium-channel.png]] | [[Image:640px-Sodium-channel.png]] | ||
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This image shows the crystal structure of the selectivity filter. <ref name= "crystal"/> | This image shows the crystal structure of the selectivity filter. <ref name= "crystal"/> | ||
=== | ===Role in infection=== | ||
There are nine different α subunits named NaV1.1 through NAV1.9. <ref name = "sod"/> Genes are SCN1 through SCN11. <ref name = "sod"/> These structures differ in their sequence and kinetics. <ref name = "sod"/> As stated above, the α subunit is necessary to the function of the channel and can function independently of the β subunit. You can find the structures and more information below. | There are nine different α subunits named NaV1.1 through NAV1.9. <ref name = "sod"/> Genes are SCN1 through SCN11. <ref name = "sod"/> These structures differ in their sequence and kinetics. <ref name = "sod"/> As stated above, the α subunit is necessary to the function of the channel and can function independently of the β subunit. You can find the structures and more information below. | ||
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* [https://en.wikipedia.org/wiki/Nav1.9 NaV1.9]: found in dorsal root ganglia. <ref name = "sod"/> | * [https://en.wikipedia.org/wiki/Nav1.9 NaV1.9]: found in dorsal root ganglia. <ref name = "sod"/> | ||
=== | ====Treatment==== | ||
==Medical Implications== | ==Medical Implications== | ||
Diseases caused by mutations in sodium channels can come in many forms. Some mutations affect skeletal, cardiac or smooth muscle, while others affect neural function. Common diseases include long QT syndrome, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, myotonia fluctuans and myotonia permanens among many others. <ref name ="dis">http://neuromuscular.wustl.edu/mother/chan.html#SCN4A</ref> | Diseases caused by mutations in sodium channels can come in many forms. Some mutations affect skeletal, cardiac or smooth muscle, while others affect neural function. Common diseases include long QT syndrome, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, myotonia fluctuans and myotonia permanens among many others. <ref name ="dis">http://neuromuscular.wustl.edu/mother/chan.html#SCN4A</ref> | ||
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Hyperkalemic period paralysis is caused by the mutations T704M, S906T, A1156T, M1360V, A1448C and/or M1592V. <ref name = "Hyper">http://neuromuscular.wustl.edu/mother/activity.html#hrpp</ref> These mutations cause periodic or permanent weakness. <ref name = "Hyper"/> Physiologically, this is a gain of function mutation. During rest after exercise, or after eating foods rich in K<sup>+</sup>, the extracellular K<sup>+</sup> increases, which mildly depolarizes the membrane.<ref name = "Hyper"/> This causes abnormal Na<sup>+</sup> channels to open, and they are unable to inactivate. <ref name = "Hyper"/> This sustained depolarization of the membrane causes even more abnormal Na<sup>+</sup> channels to open and ultimately this leads to loss of excitability and weakness. <ref name = "Hyper"/> This symptom usually appears within the first decade of life and can be aggravated by exercise, cold, potassium loading, fasting or pregnancy. <ref name = "Hyper"/> Attacks are usually brief and do not need treatment. <ref name = "Hyper"/> | Hyperkalemic period paralysis is caused by the mutations T704M, S906T, A1156T, M1360V, A1448C and/or M1592V. <ref name = "Hyper">http://neuromuscular.wustl.edu/mother/activity.html#hrpp</ref> These mutations cause periodic or permanent weakness. <ref name = "Hyper"/> Physiologically, this is a gain of function mutation. During rest after exercise, or after eating foods rich in K<sup>+</sup>, the extracellular K<sup>+</sup> increases, which mildly depolarizes the membrane.<ref name = "Hyper"/> This causes abnormal Na<sup>+</sup> channels to open, and they are unable to inactivate. <ref name = "Hyper"/> This sustained depolarization of the membrane causes even more abnormal Na<sup>+</sup> channels to open and ultimately this leads to loss of excitability and weakness. <ref name = "Hyper"/> This symptom usually appears within the first decade of life and can be aggravated by exercise, cold, potassium loading, fasting or pregnancy. <ref name = "Hyper"/> Attacks are usually brief and do not need treatment. <ref name = "Hyper"/> | ||
