User:Alex Pennington/Sandbox 1: Difference between revisions
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==Nicotinic Acetylcholine Receptor== | ==Nicotinic Acetylcholine Receptor== | ||
[[Image:NR.png]]The nicotinic acetylcholine receptor is a key protein in neuronal communication. This protein effectively converts neurotransmitter binding into a membrane depolarization event. The protein combines neurotransmitter binding sites, specifically [[acetylcholine]], with a cationic ion channel, specifically sodium (Na). | [[Image:NR.png]] | ||
The nicotinic acetylcholine receptor is a key protein in neuronal communication. This protein effectively converts neurotransmitter binding into a membrane depolarization event. The protein combines neurotransmitter binding sites, specifically [[acetylcholine]], with a cationic ion channel, specifically sodium (Na). | |||
== Structure == | == Structure == | ||
The receptor is a transmembrane pentameric glycoprotein. It has a weight of approximately 300,000 Daltons. It cylindrical in appearance by electron microscopy approximately 16nm in length and 8nm in diameter. The main ion channel is composed of a water pore that runs through the entire length of the protein. If viewed from the synaptic cleft, the protein will look like a pseudo-symmetrical rosette shown in the picture below composed of 10 different aplha and 4 different beta subunits. | |||
=== Physiology | [[Image:NR1.jpg]] | ||
=== ACh Binding Sites === | |||
This protein carries anywhere from 2 to 5 [[acetylcholine]] binding sites which are located at the interface between two subunits. Each subunit contributes 3 loops to the binding site. There is also a "principle" side and a "complimentary" side of the subunits. The principle side binding nicotine with a high degree of specificity and the complimentary side binding a wide variety of acetylcholine like molecules. | |||
=== Ion Channel === | |||
The ion channel of the protein is a 20 membered alpha helix bundle. This channel also contributes to the receptor function in three critical aspects: it contains a gating mechanism, it contains a water pore to stabalize ions, and it has a selectivity filter for ion charge. As with most transmembrane alpha helix bundles, it is hydrophobic around the edges to effectively be supported within the membrane, and it is hydrophilic on the inner portion to transport charged ions. | |||
== Physiology == | |||
The receptor is a cylidrically-shaped protein. It is embedded in the cell wall of post synaptic nerves at the skeletal neuromuscular junction. The receptor acts as a chemically controlled sodium (Na) channel also known as a [[ligand gated channel]]. | The receptor is a cylidrically-shaped protein. It is embedded in the cell wall of post synaptic nerves at the skeletal neuromuscular junction. The receptor acts as a chemically controlled sodium (Na) channel also known as a [[ligand gated channel]]. | ||
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=== Clinical Findings === | === Clinical Findings === | ||
Findings due to nicotinic stimulation from [[cholinesterase inhibitors]] | |||
* Neuromuscular junctions of skeletal muscles | |||
** Fasiculations and myotonic jerks | |||
** Weakness and paralysis of the muscle | |||
* Sympathetic nervous system | |||
** Hyperglycemia and ketosis | |||
** Hypertension | |||
** Leukocytosis | |||
** Pupillary dilation | |||
** Sweating | |||
** tachycardia | |||
** Urinary retention | |||
Below is a mnemonic for remembering nicotinic signs of [[cholinesterase inhibitor toxicity]] | |||
'''M'''onday '''M'''ydriasis (pupil dilation) | |||
'''T'''uesday '''T'''achycardia | |||
'''W'''ednesday '''W'''eakness | |||
T'''h'''ursday '''H'''ypertension | |||
'''F'''riday '''F'''asciculations | |||
== References == | == References == | ||
1. Cholinesterase Inhibitors: Including Insecticides and Chemical Warfare Nerve Agents, ''Agency for Toxiz Substances and Disease Regulation'' '''accessed 5/2/14''' | |||
2. Pierre-Jean Corringer and Jean-Pierre Changeux (2008) Nicotinic acetylcholine receptors. Scholarpedia, 3(1):3468. | |||
3. Adcock C, Smith GR, Sansom MS. The nicotinic acetylcholine receptor: from molecular model to single-channel conductance. Eur Biophys J. 2000;29:29–37. |