SNS and muscle Flashcards
Muscle structure
- Various layers of complexity
- 150 muscle fibres in bundles: Fasiculi
- Muscle fibre membrane: sarcolemma
- Muscle Fibre: 100s- 1000s myofibrils
- Sarcoplasm: glycogen, fat, enzymes, mitochondria
- Sarcoplasmic reticulum: Ca2+ release
- Anisotropic band: high density (thick)
- Isotropic band: actin filaments
Sliding filament model
1950s
Calcium ions bind to troponin on tropomyosin, exposes myosin-binding sites. Myosin-head binds to form a cross bridge.
ATP is needed for myosin to enter its high configuration state.
Once ATP is hydrolysed, there is a power stroke and the thin filament slides towards the centre of the sarcomere.
The somatic nervous system
- Part of the PNS
- Provides voluntary control over the skeletal muscle.
- Efferent neurons that innervate muscle = Motor neurons
- Upper MNs in the brain connect with lower Motor neurons in the spinal cord – signal to muscle.
Cholinergeic receptor
Muscarinic (primarily CNS, GPCR, slow)
Nicotinic (neuronal /NMJs, Fast)
Duchenne muscular dystrophy
- DMD most common severe form of childhood muscular dystrophy (1:5000 males). Mutated gene: Dystrophin
- Skeletal + cardiac
- Unable to walk by 10- 12 yrs, Death by early to mid 20s (heart failure)
- Connects actin filaments to the sarcolemma, required for mechanical stability
- Lack of dystrophin causes dysfunction of sarcolemma stretch = ion pores open and increased intracellular Ca2+.
- Degradation of structural proteins, CK lost from the cell into blood (indication of muscle damage). CK required for ATP
Motor neuron disease
Motor neuron disease (MND) is a group of disorders that selectively affect motor neurons, the cells that control voluntary muscle activity including speaking, walking and swallowing.
In the US, ALS is frequently used as a blanket term for entire spectrum of MND
Different Motor neuron disease
Amyotrophic Lateral
Sclerosis (ALS)
Progressive Muscular
Atrophy
Primary Lateral
Sclerosis
Progressive Bulbar
Palsy
Pseudobulbar
Palsy
Other
Amyotrophic lateral sclerosis (ALS)
ND disease affecting MNs, severe disability leading to death from respiratory failure (Lower MNs). • Affects 1:200,000 • 5-10% familial -30-40% C9orf72 -15-20% SOD1 -5% TARDBP -5% FUS Sporadic probably caused by a combination of environmental and genetic factors – largely unknown
Myathenia Gravis
Chronic autoimmune NMD results in skeletal muscle weakness and fatigue.
1-7 in 10,000
Young women (20-30 yrs) and older men (50-60 yrs)
-3:2 (F:M)
Body makes antibodies against AchRs at NMJs
Blocks AchRs, increases AchR degradation and causes impaired signal transduction
Treatment with Acetyl cholinesterase Inhibitors or immuno-suppressants (prevent AchR degradation)
What is titin?
Giant molecular spring
What is a sarcomere?
Contractile unit
Motor neurons and contraction
- Single fibre contracts completely or not at all
- Motor units can innervate few to hundred fibres
- Can regulate strength of muscle contraction by varying how many activated Motor units
What is the motor unit?
• Motor unit: single Motor unit and all muscle fibres it controls
Describe the neuromuscular junction?
Action potential reaches the synaptic terminal. ACh is released into the synaptic cleft and binds to the receptors on the plasma membrane of the muscle cell.
This leads to the muscle cell being depolarized and causes the sarcoplasmic reticulum to release Calcium ions into the cytosol.
These calcium ions then bind to troponin, tropomyosin moves and a contraction can occur.
Graded muscle contractions
A single Action potential will produce twitch lasting 100 msec = single twitch
If 2nd arrives before muscle has relaxed, summation of two twitches = greater tension
