Neuromuscular Junction by

2024-10-31 14:18:19 UTC

Mitochondria is the powerhouse of the cell

RyRs are located in SR

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RYRs located on SR

LO1

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Calcium storage in the ER

RyRs are in sarcoplasmic reticulum

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RyRs are associated with severe skeletal muscle disorders or triggered cardiac arrhythmias

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Sarcoplasmic reticulum

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Ca can act as a ligand or second messenger

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Calcium!

LO1

faithfulturtle — 2024-10-31 14:18:42 UTC

Ca2+ important! Need Ca2+

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Sarcoplasmic reticulum is the calcium credit union

needs ATP

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ATP depletion-> Calcium stores-> Arrythmias

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RyR arenegatively affected by low Ca++

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Cardiac receptors, sarcoplasmic reticulum, arrhythymia

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Mitochondria protects the cell from calcium

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RYR and arrhythmias

Depletion of ATP affects Ca2+ storage

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Calcium is a ligand or 2nd messenger

LO 1

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IP3R associated with GPCR (metabo)

RyR associated with LTCC (iono)

SARCOPLASMIC RETICULUM

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Calmodulin

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Is low cortisol associated w/ high catecholamines?

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Learning Objective 1

brianamgutierrez — 2024-10-31 14:18:58 UTC

RyR and IP3R located in the sarcoplasmic reticulum

LO1

2024-10-31 14:18:59 UTC

RyRs are linked to LTCC channels that cause influx of Calcium that will affect the activity of the cell by releasing more calcium. IP3Rs require IP3 for activation through GPCR activation

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depletion of ATP or calcium can cause dysfunction

calcium

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arrhythmia is related to calcium not enough

IP3Rs connected to GPCRs

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Found in ER/SR

faithfulturtle — 2024-10-31 14:19:06 UTC

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IP3R require inosol 1, 4, 5 triphosphate

Sarcoplasmic Reticulum!

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IP3 is second messenger

L.O. 1

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Cardiac arrhythmias are followed by low cortisol and abnormal catecholamines

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RyR in SR. Cardiac arrhythmia = fast Ca2+ release

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Located in SR; regulated by L type Ca channel; associated with severe skeletal muscle disorders or triggered cardiac arrhythmias; regulated by calcium, Mg, ATP, CaM, kinase/phosphatase

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RYRs and IP3R both use Ca2 and both are on SR

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Sr has RYR ip3r

RyRs coupled to L-type Ca channels. IP3R coupled to GPCR

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if ca or ryr messed up, cardiac issues

LO1

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RyR dependent on chaRge,

L.O. 1

amberhowell2 — 2024-10-31 14:20:00 UTC

Calcium is needed for muscle contraction. Calcium can be stored in the ER or SR. We need alot of calcium in our cells. If there is no ATP, calcium storage is modifided. Ca2+'s credit union is the endoplasmic reticulum.

2024-10-31 14:20:46 UTC

Present in the SR. L-type calcium channels and IP3 as a second messenger. Dysregulation of calcium levels can lead to cardiac arrhythmias. This can lead to low cortisol or abnormal catecholamines.

2024-10-31 14:26:34 UTC

Depolarization to release calcium from SR. Calcium binds to troponin to move it out of the way!

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when ACh binds to receptor, it triggers depolarization of muscle fiber. Ca2+ channels open and Ca2+ enters --> muscle contraction

LO2

2024-10-31 14:27:08 UTC

Depolarization in the SR causes release of Calcium which binds to troponin and allows for a contraction to occur. Pathologies can arise when there is low ATP in the cell or the body produces antibodies against calcium channels.

2024-10-31 14:27:19 UTC

Motor neuron and muscle fiber synapse at the NMJ >Ach binds receptors and causes action potential to move through the T tubule > Ca is released from the SR > Ca binds to troponin, which moves tropomyosin out of the way > myosin binds actin and causes contraction > ATP is used to clear Ca when contraction is over and reset

LO2

faithfulturtle — 2024-10-31 14:29:41 UTC

Action potential in T-tubule --> depolarization --> Ca2+ channels open in SR --> Ca2+ moves to cell cytosol --> Ca2+ binds troponin --> contraction --> Ca2+ back to SR by ATP pump --> relaxation

LO2

faithfulturtle — 2024-10-31 14:30:11 UTC

NMJ - synapse between motorneuron and muscle fiber

ACh synthesis

faithfulturtle — 2024-10-31 14:32:46 UTC

from choline and acetyl CoA --> broke down by AChE

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Ca2+ pumped back into SR by ATP-dependent pumps

ACh is released from motor neuron is picked up by AChR on the muscle causing depolarization of the muscle cell

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Actin blocked by tropomyosin at rest Ca2+ released then binds troponin allowing muscle contraction, Ca2+ is then moved back to SR - ATP dependent - muscle relaxation

Nicotinic ACh Receptors

faithfulturtle — 2024-10-31 14:34:23 UTC

muscle-type and neuronal type

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there are two types of nicotinic acetylcholine receptors: muscle-type and neuronal-type

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Lo3

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Quantal is the amount of Ach required to reach a muscle contraction

L.O. 3

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Quantal is a measurement for the effective amount of ACh to get a muscle contraction

IP3 Receptors and Ryanodine receptors

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Muscle Ach receptors 5 subunits

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ACh deficits lead to Alzheimer's disease

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Depolarization- Ca releases from sarcoplasmic reticulum- Ca binds to troponin- muscle contraction!!

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Ca+ enters the cell through the LTCC then binds to RyR to release Ca+2 from the SR to allow for MUSCLE CONTRACTION

Mitochondria is the powerhouse of the cell

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Acetylcholinesterase inhibitor for Alzheimer’s

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AchE is needed to clear Ach from the synapse. IP3 and RyR work together in response to nervous stimulation to cause muscle contraction via calcium release

LO3

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muscle type channels found at NMJ

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Open ca2+ channels in SR membranes so calcium can diffuse into cytosol

Mitochondria is the powerhouse of the cell

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LO2

brianamgutierrez — 2024-10-31 14:36:04 UTC

Ach is released from the neurons. Ach binds to the Ach R triggers depolarizes the muscle fibers. Calcium is going to open, and cause m. contraction

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Don't smoke

LO2

2024-10-31 14:36:18 UTC

We can have many problems in the neurological pathway from the neuron until the contraction of the muscle.

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Ach from motor neuron thru synapse opens voltage gates channels enacting muscle contraction via RyR and IP3 alongside , reuptaken by ache

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NMJ is site for transmission of APs from nerve to muscle it is also site of action for pharmacological drugs

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Quantal is the amount of ACh needed to elicit an action potential

2024-10-31 14:36:36 UTC

RYR and IP3 receptors are important. Ach will bind, triggering depolarization, opening Ca2+ channels, allowing entry into the cytoplasm, binding to troponin and leading to contraction. Calcium will be pumped back into the SR using ATP to lead to muscle relaxation.

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Ach broken down by acetylcholinesterase

Lo3

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Treat Alzheimer's with AChE inhibitors to keep the available Ach in the synaptic cleft

LO3

2024-10-31 14:37:05 UTC

Smoking is bad. Will interact with your nicotine receptor and MESS IT UP :)

2024-10-31 14:37:43 UTC

Choline and acetyl CoA make acetylcholine. Broken down by acetylcholinesterase, and choline will be transported back to the axon terminal to make more. QUANTAL

L.O.3

2024-10-31 14:38:34 UTC

Lambert-Eaton is a problem with ca2+ gated channels

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MG: autoimmune disorder. Abs -> reduction in function of RYR receptors

low calcium quantal release contributes MG

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MG: antibodies destroy N receptors, loss of motor function (mainly eye)

low calcium release... not necessarily low calcium (i think)

In MG there are antibodies against ryanodine receptors and nicotinic receptors

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main symptom of myasthenia gravis is ocular muscle weakness

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MG

faithfulturtle — 2024-10-31 14:43:20 UTC

antibodies against RyR and IP3R receptors --> no depolarization --> no muscle contraction --> ptosis and muscle weakness; specific to MG

2024-10-31 14:43:35 UTC

Ocular muscle weakness due to antibodies against the receptor is the main indicator of myasthenia gravis

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MG: Ocular muscle weakness the most common presenting symptom

Low quantal release and ineffective receptors leading to no depolarization and muscle contraction

Antibodies against the ryanodine receptors

LO4

brianamgutierrez — 2024-10-31 14:44:09 UTC

MG main sx is ptosis, caused by antibodies against Ach R and Ach

MG: not enough Ach and receptors are not as effective (due to antibodies); leads to LACK of depolarization of muscle fibers; will see ocular muscle weakness; facial nerve is affected

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LES has antibodies agains voltage gated calcium channels which will cause reduction in ACh release

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LES: 50% have lung cancer,

due to voltage gated ca channel

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LES: low levels of Ach and Ca2+ that are not sufficient to cause normal muscle contraction causing muscle weakness

LES

faithfulturtle — 2024-10-31 14:46:01 UTC

antibodies against voltage-gated Ca2+ channels; low ACh and Ca2+; muscle weakness, small cell lung carcinoma in 50%; Proximal triad: weakness, depressed reflexes; autonomic dysfunction

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In botulism, BoNT blocks presynaptic ACh release and inhibits muscle which will cause flaccid paralysis

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BoNT targets SNARE which is required for Ach release so without SNARE there is no depolarization or contraction of muscle cells.

2024-10-31 14:49:50 UTC

Myasthenia gravis - autoimmune; ocular muscle weakness/ptosis - one of first symptoms; antibodies against ACh R; bilaternal weakness/paralysis; CN VII; low quantal calcium release and decreased binding AChR and decreased depolarized of muscle; also antibodies against ryanodine receptor - specific for myasthenia gravis; Lambert Eaton Myasthenic syndrome - smoking and small cell lung cancer - antibodies against voltage gated calcium channel; reflexia; autonomic disruption; dry mouth; proximal muscle weakness; botulism - clostridium neurotoxin; common in infants; diffuse and flaccid paralysis; prevents fusion of NT vesicles; toxin crosses mucosal barriers to blood stream; end result - decreased release of ACh;

Botulism

faithfulturtle — 2024-10-31 14:49:59 UTC

BoNT targets SNARE --> no ACh --> blocks release and inhibits muscle contraction --> flaccid paralysis

2024-10-31 14:50:24 UTC

botulism: opposite symptoms than tetany.

due to bacteria
flaccid paralysis d/t inhibiting contraction

don't get botox?

brianamgutierrez — 2024-10-31 14:50:45 UTC

botulism - targeting SNARE

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Botulism.

Clostridium botulinum (anaerobic gram positive, spore forming)

Infant botulism - lack of robust immune system

Botulinum neurotoxin (BoNT)

Travels to and binds presynaptic nerve terminals

Targets SNARE required for fusion of Ach containing vesicles

No exocytosis of Ach

Inhibits muscle contraction.

Flaccid paralysis.

2024-10-31 14:51:00 UTC

mechanism of LES is antibodies against voltage-gated calcium channels

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MG: antibodies, protosis

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Lambert Eaton- lung cancer, dry mouth, muscle weakness

2024-10-31 14:52:19 UTC

Myasthenia Gravis: RyR and nAChR are implicated in the mechanism of this disease