Muscle Physiology 1 Flashcards
Explain communication at NMJ
- Action potential arrives at terminal bouton
- Voltage-gated calcium channels open
- Calcium enters cell triggering release of ACh
- ACh diffuses across cleft and binds to nicotinic receptors on motor end plate
- ACh triggers opening of channels for small cations sodium and potassium
- Net movement of positive charge in—> depolarization
- End plate potential= EPP
- EPP> EPSP
- EPP causes action potential in muscle cell
- Action potential spreads through muscle causing contraction
Why is EPP (End plate potential) special?
Muscle AP needs to be above threshold, to propagate
What is the clinical correlation of neuromuscular junction?
- weakness and fatigue of the skeletal muscles. In one form, the extraocular muscles are primarily affected.
- Caused by the formation of circulating antibodies to the Nicotinic acetylcholine receptors.
- Weakness improves after a period of rest or after administration of acetylcholinesterase inhibitors
This leads to the tensilon test
What causes myasthenia Gravis?
Autoimmune damage of nicotinic cholinergic receptors- tensilon test
What causes Lambert-Eaton syndrome?
- Muscle weakness is caused by an autoimmune attach against Ca2+ channels in the nerve endings at the NMJ.
- Decreased Calcium influx at NMJ—> decreased ACh release.
- Proximal muscles of the lower extremities are primarily affected, producing a waddling gait and difficulty raising the arms.
- Difference with myasthenia Gravis
How does the Latrotoxin combat the antibodies in lambert Eaton?
Latrotoxin STIMULATES voltage gated calcium channels while the antibodies destroy them.
Latrotoxin: the venom of the black widow spider, it opens presynaptic Ca2+ channels resulting in excess ACh release—> profound muscle contraction —> muscle spasms, muscle pain, and abdominal rigidity
Explain the significance of Botulinum toxin / Botulism/ Botox
- Produced by the bacterium Clostridium botulinum. Food poisoning by ingestion of this organism can cause Botulism.
- Protease that prevents release of ACh vesicles from the NMJ
- Symptoms include weakness of muscles Innervated by cranial nerves, blurred vision, flaccid paralysis
- In small doses, it is used in cosmetic treatment of Botox
Summarize NMJ blockers as muscle relaxants
- Tubocurarine and is a Nm receptors antagonist and used as a skeletal muscle relaxant
- Curareis a plant-derived alkaloid, used as arrows/blow dart poison. It is a competitive inhibitor of Nm
Contrast resting and contracting muscle
Resting muscle
- Intracellular calcium concentration very low(10^-9 M or nM)
- Majority Ca2+ stored in sarcoplasmic reticulum (SR)
- Ca2+ bound to SR proteins e.g., calsequestrin
Contracting muscle
- Muscle depolarization —> Ca2+ release from SR
- SR ONLY source of Ca2+ for contraction (skeletal muscles)
- Intracellular [Ca2+] increased (>10^-6M or um)
What are the steps of excitation-contraction relaxation
- Somatic motor neuron releases ACh a neuromuscular junction
- Net entry of Na+ through ACh receptor-channel initiates a muscle action potential
- Action potential in t- tubule alters confirmation of DHP receptor.
- DHP receptor opens RyR Ca2+ release channels in sarcoplasmic reticulum , and Cax2+ enters cytoplasm
- Ca2+ binds to troponin, allowing actin-myosin binding
- Myosin heads execute power stroke.
- Actin filament slides toward center of sarcomere
- Sarcoplasmic Ca2+-ATPase pumps Ca2+ back into the SR
- Decrease in free cytosolic Calcium concentration to unbind from troponin
- Tropomyosin recovers binding site. When myosin heads release, elastic elements pull filaments back to their relaxed position
What creates the end plate potential?
Depolarization of muscle fiber membrane creates an end plate potential
What is a muscle twitch?
A single contraction relaxation cycle
What is a latent period?
The short delay between the muscle action potential and beginning of muscle tension development
-Time required fir calcium release and binding to Troponin
What is the clinical correlation of malignant hyperthermia?
Excitation contraction coupling
-mutations or Dysregulation of Ca2+ release channels in muscle (ryadone receptors)
- patients with condition display normal muscle function under normal conditions
- However, certain anesthetic agents or in rare cases exposure to high environmental heat or strenuous exercise can trigger an abnormal release of Ca2+ from the sarcoplasmic reticulum in the muscle cell, resulting in sustained muscle contraction and heat production.
What is this treatment of malignant hyperthermia?
Daunt role need directly interferes with muscle contraction by binding RyR receptors
