Muscle Contraction and Dysfunction Flashcards
What are the three types of muscle?
→ Skeletal
→ Smooth
→ Cardiac
How many muscle fibres are there in bundles and what are they called?
→ fasciculi
What is the muscle fibre membrane called?
→ Sarcolemma
What is a muscle fibre made from?
→ 100s-1000s of myofibrils
What does the sarcoplasm contain?
→ glycogen
→ fat
→ mitochondria
→ enzymes
What does the sarcoplasmic reticulum do?
→ Release Ca2+
What is a sarcomere?
→ a contractile unit
What is the anisotropic band?
→ high density band
What is the isotropic band?
→ actin filaments
→ titin
Describe how the actin myosin binding sites are exposed
→ Troponin forms a complex with tropomyosin
→ When Ca2+ binds to troponin it causes a conformational change to the troponin
→ This causes the tropomyosin to move
→ It exposes the actin-myosin binding sites
→ Allows the myosin head to bind to the actin
Describe the sliding filament theory?
Motor neuron stimulates a muscle to contract
→ Release of Ca2+ into the muscle cell
→ myosin has a globular head that ATP binds to
→ ATP is hydrolysed
→ Phosphate bond breaking provides energy for the power stroke
→ releases ADP and an inorganic phosphate
→myosin head is cocked
What does the somatic nervous system do?
→ Provides voluntary control over skeletal muscle
What are motor neurons?
→ Efferent neurons that innervate muscle
What does one motor unit include?
→ A single motor neuron and all the muscle fibres it controls
How do motor units regulate the strength of contraction?
Varying how many activated motor units are recruited
Describe what happens at a neuromuscular junction when a stimulus is applied?
→ A stimulus from the brain causes an action potential
→ ACh is released
→ ACh binds to receptors and causes depolarisation of the membrane
→ depolarisation moves along the membrane and through T tubules
→ T tubules enter the muscle and cause depolarisation of the SR
→ SR releases Ca2+
→It is released into the cytosol and causes contraction of muscle fibres
What are the 2 types of cholinergic receptor?
→ Muscarinic
→ Nicotinic
How many molecules of ACh bind to a nicotinic receptor?
→ 2
What does a single action potential produce?
→ a single twitch
How do you get greater tension within a muscle?
→ if an additional action potential arrives before the muscle relaxes from the first action potential
→ There is summation of the two and greater contraction
What is tetanus?
→ When the rate of action potentials is so high that the muscle doesn’t relax between stimuli
What is the mutated gene in DMD? (duchenne muscular dystrophy)
→ dystrophin
→allows for cell membrane to be stabilised as contraction happens
What is the function of dystrophin?
→ Connects the sarcomere to the plasma membrane
Where is the dystrophin gene located?
short arm of the X chromosome
What is the difference between Duchenne and Becker disease?
→Duchenne=total loss of dystrophin
→Becker= reduced or dysfunctional dystrophin
What are the effects of dystrophic myopathy diseases?
→increased permeability to macromolecules
→abnormal permeability is made worse by mechanical stress
→Muscle fibre necrosis, fibrosis and fat inflitration
What happens to people with DMD?
→ unable to walk by 10-12 years
→ death by early to mid 20s
What are the effects of a lack of dystrophin?
→ Dysfunction of the sarcolemma stretch
→ ion pores open and there is increased intracellular Ca2+
→ membrane gets torn
What is an indication of muscle damage in DMD?
→ CK (creatine kinase) is lost from the cell and goes into the blood
→ degradation of structural proteins
what is creatine kinase needed for?
→ recycling of ATP
What enables patients with DMD to walk for longer?
→ corticosteroids like prednisone
What is myasthenia gravis?
→chronic autoimmune motor neuron disease
→ Body makes antibodies against AChRs at neuromuscular junctions
→ targets alpha-1 subunit
How do you treat myasthenia gravis?
→ AChesterases inhibitors
What toxin does myasthenia gravis mimic?
botulinum toxin
What is multiple sclerosis?
→Immune attack of myelin
→Leaky blood brain barrier
→Sclerotic lesions
What are the manifestations of MS?
→Numbness →Tingling →Speech problems →Visual problems →Debilitating muscle weakness
What cells produce myelin?
→glial
→non-neuronal
What are glial cells called in the CNS and PNS?
CNS=form the myelin sheath are called oligodendrocytes
PNS=called Schwann cells
What is the AIS?
Axon initial segment
What is the function of AIS?
→Sodium entry through channels at the AIS
→serves as the site of action potential firing and helps to maintain neuron polarity.
What is the role of nodes of Ranvier?
Rejuvenation of excitation
→Concentration of voltage gated sodium channels
What is the purpose of myelin sheath?
→Prevents charge leakage and dissipation of excitation
What are the features of non-dystrophic myotonias?
→Delayed relaxation of the muscle after voluntary contraction or mechanical stimulation.
→highly organized repetitive electrical activity of the muscle fibres
What mutations characterise NDM?
SCN4A gene(codes for a VGSC)
Give examples of NDMs?
Potassium-aggravated myotonia (PAM),
→Paramyotonia congenita (PMC)
→Hyperkalemic periodic paralysis (HyperPP),
→Hypokalemic periodic paralysis (HypoPP),
→A form of congenital myasthenic syndrome (CMS)
What do mutations in NDM cause?
→decreased rate of channel inactivation
→increased rate of recovery from inactivation
→slower channel deactivation
What are some NDMs due to?
loss of Cl channel (CLC-1)
→Less Cl channel activity
→Prolonged contraction
What does NDM result in?
→ paralysis
Describe the activation of VGSC?
→When the membrane potential depolarises the voltage sensor domains move out of the plain of the membrane
→allows sodium ions to pass through the pore
→sodium flow is brief because a few ms later the so called inactivation ‘lid’ part of the channel then moves to and blocks the channel pore
→no flow of sodium but the voltage sensors are still poking up so the channel is not closed but is INACTIVATED
Describe VGSCs
→formed from one large protein comprised of 4 repeated regions and each has 6 transmembrane domains
→4th transmembrane domain of each region is packed with positively charged amino acids and is known as the voltage sensor.
How are VGSCs implicated in NDMs?
mutations to the gene that affects the property of inactivation will allow for longer / more persistent sodium influx.
