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Year 2 - T3 Theme 2 > Physiology of muscle contraction - coordination, force and plasticity > Flashcards

Physiology of muscle contraction - coordination, force and plasticity Flashcards

1
Q

How does troponin function

A
  • 4 Ca2+ bind to troponin C ( C = calcium binding)
  • TnC changes conformation
  • Conformational change in TnC ‘shuts off’ TnI tropomyosin-troponin leaves F-actin groove unmasks the myosin binding site on actin
  • Next myosin heads make cross bridges (cycling) to actin
  • Myosin breaks down ATP
  • Myosin pulls thin filaments
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2
Q

How many Ca2+ ions bind to troponin C in the heart

A
  • In heart TnC only binds to 3 Ca2+ ions
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3
Q

What is total TnI a marker for

A
  • Marker for total muscle breakdown
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4
Q

What is cardiac TnI a marker for

A
  • Marker for myocardial infarct
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5
Q

Cross bridge cycling

A
  • Molecular cycle of actin-myosin interaction
  • Mechanism of contraction at molecular level
  • Contraction depends on binding of myosin heads to thin filaments (actin) at specific binding sites
  • In resting state of sarcomere, myosin heads are blocked from binding to actin by tropomyosin, which occupies the specific binding sites (in F-actin double helical groove)
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6
Q

Force generation vs sarcomere length

A

Increase in overlap of thin and thick filaments leads to the most force generation

Greatest force generation therefore occurs when sarcomere is at an optimal length where there is maximum overlap

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7
Q

Cross bridge cycle steps

A
  1. Myosin releases actin
  2. Myosin head cleaves ATP
  3. Myosin binds actin
  4. Power stroke
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8
Q

Where is creatine found

A
  • Creatine is found in muscle fibres

- Phosphorylated to creatine phosphate, this is how energy is stored in muscle

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9
Q

What happens to creatine phosphate when cross bridge cycling occurs

A
  • When cross bridge cycling hydrolyses ATP to ADP + Pi, creatine donates a high energy phosphate to ADP restoring it to ATP
  • ATP levels must be kept stable - buffering and regeneration
  • The reaction is catalysed in both directions by the enzyme creatine phosphokinase
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10
Q

Creatine vs creatinine

A
  • Creatine is a small molecule that can accept high energy phosphate bonds from ATP
  • Creatine-phosphate is the above molecule after phosphate has been added to it
  • Creatine-phosphokinase (CPK) is the enzyme that adds phosphate to creatine (this is a plasma marker of muscle destruction. It is a large molecule detected by antibodies)
  • Creatine-kinase (CK) is just another name for creatine phosphokinase
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11
Q

What is creatinine a diagnostic marker of

A
  • Creatinine is a diagnostic marker of kidney function

- It is a breakdown product of creatine

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12
Q

How does Ca2+ trigger contraction

A

There are two Ca2+ gradients

  • Extracellular vs cytosolic free Ca2+
  • SR vs cytosolic free Ca2+
  • Efflux of Ca2+ from sarcoplasmic reticulum to cytoplasm provides most of calcium
  • Calcium entering cell from outside provides only small fraction of calcium needed for contraction
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13
Q

What causes an increase in Ca2+ levels prior to contraction

A
  • Depolarisation –> increase in Ca2+
  • ACh –> depolarisation
  • Active nicotinic AChR –> net inward current depolarisation spread via T-Tubules
  • Local action potentials trigger Ca2+ efflux from terminal cisternae (across membrane of sarcoplasmic reticulum, into the fibre cytoplasm)
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14
Q

Features of ryanodine receptors and SERCA receptors

A

Ryanodine receptor (RyR) - In SR membrane. Releases Ca2+ From SR. Triggered by voltage sensor on Ca2+ channel

SERCA - In SR membrane. Pumps Ca2+ back into SR. Needs ATP

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15
Q

Tetany - molecular basis

A
  • A single AP –> Ca2+ release from SR –> twitch
  • Ca2+ ions are rapidly pumped back into SR –> end of twitch
  • Frequent APs –> insufficient Ca2+ resequestration –> summation of contraction
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16
Q

Types of muscle fibres

A
  • Slow twitch (type I - ‘red’ - oxidative, small diam) High myoglobin, many mitochondria
  • Fast twitch (type II - ‘white’ - nonoxidative, wide diam.) Lower myoglobin, increase in energy from glycolysis
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17
Q

How do fibre types differ

A
  • Aerobic (slow) vs anaerobic
  • Faster calcium re-uptake (fast)
  • Maximum tension produced (fast)
  • Fatigue resistance (slow)
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18
Q

Basis of muscle fibre types

A

Slow ————–> Fast
Type I, IIA, IIX, IIB
Slow sustained —-> fast intermittent/precise

19
Q

Distribution of fibre types

A
  • Muscles contain mixtures of fibre types. Composition depends on muscle action
  • Soleus = 80% Type I (Slow), 20% Type IIA
  • Vastus lateralis = mixture of type I, IIA, IIX
20
Q

What do proportions of fibre types depend on

A

Proportions depend on physical fitness:

  • Inactive
  • Moderately active
  • Endurance athlete
  • Anaerobic athlete
21
Q

Features of Type I muscle fibres

A 
Sub-name - Slow oxidative 
ATP generation - Aerobic 
Contraction rate - Slow 
Fatigue resistance - High 
Fibre diameter - Small 
Myoglobin - High 
Mitochondria - Many 
Capillaries - Many 
Fuel for storage - Triglycerides
22
Q

Features of Type IIA muscle fibres

A 
Sub-name - Fast oxidative-glycolytic 
ATP generation - Aerobic/anaerobic 
Contraction rate - Fast 
Fatigue resistance - Intermediate
Fibre diameter - Intermediate 
Myoglobin - High 
Mitochondria - Many 
Capillaries - Many 
Fuel for storage - Creatine-phosphate. Glycogen
23
Q

Features of Type IIB (IIX) muscle fibres

A 
Sub-name - Fast glycolytic 
ATP generation - Anaerobic
Contraction rate - Fastest
Fatigue resistance - Low 
Fibre diameter - Large 
Myoglobin - Low 
Mitochondria - Few 
Capillaries - Few
Fuel for storage - Creatine-phosphate. Glycogen
24
Q

Co-ordination of muscle contraction

A

3 types of co-ordination

Motor units - recruitment and size principle

Tetany

Fusion of myocytes into long myofibres

25
Q

Definition of a motor unit

A
  • A single alpha motor neuron and muscle fibres it innervates
26
Q

How does the motor unit function

A
  • Functions as a single contractile unit of skeletal muscle

- All muscle fibres in a single motor unit are of the same type (e.g. slow oxidative, fast oxidative, fast glycolytic)

27
Q

Motor units: Variety

A
  • In large muscles responsible for powerful gross contractions, a single motor neuron may synapse on 1000 fibres
  • In small muscles mediating precision movement, a single motor neuron may synapse with as few as 2-3 muscle fibres
  • Type and function of the lower motor neuron determines the muscle fibre,
  • There are different sorts of motor units in a single muscle
28
Q

Contraction: force generation

A

Isometric - generates a variable force while length of muscle remains unchanged

Isotonic - generates a constant force while the length of the muscle changes

29
Q

Using an example, describe the types of force generation

A

• Using example: picking up a drinking glass
• stage 1: isometric – force increases, joint does not move
○ Muscle Force < force of gravity –> force increases
§ biceps and brachioradialis generate force by isometric contraction as muscles have not yet shortened

• stage 2: isotonic – force remains the same, arm moves
○ Glass moves upward in response to force
§ an isotonic contraction starts as the force generated by the muscles overcomes gravitational and inertial forces keeping glass on the table

  • Glass starts to rise as the muscles shorten and the elbow bends and force generated by the muscle is constant as the glass is moving
30
Q

Types of muscular force generation

A
  • Concentric - force during contraction - tossing a ball into air
  • Eccentric (negatives) - force during muscle elongation (eg when ‘braking’ or when the weight of the object is overwhelming - catching a ball
  • Both types of force generation can occur in one behaviour
  • Proprioception controls force generation based on length and stretch
31
Q

What happens as the initial isometric contraction occurs

A

As the initial isometric contraction occurs:

  • More and more motor units are recruited starting with smaller ones and progressively adding larger ones
  • Allows fine gradation of force for small movements

In drinking glass example -
More and bigger motor units recruited until the glass starts moving and the contraction becomes isotonic

32
Q

Upper vs Lower motor neuron disease

A

Lower motor neuron disease:

  • Weakness
  • Muscle atrophy

Upper motor neuron disease:
- Spasticity, hypertonia

33
Q

What is a lack of patellar reflex called

A
  • Westphal’s sign
34
Q

Features of stretch reflex

A
  • Controls muscle length
  • Increases muscle force
  • Can shorten muscle when it is too long for current neural drive
  • Sensory = intrafusal fibres(inside sheath)
  • Contraction = extrafusal fibres
35
Q

Example of a stretch reflex

A
  • Patellar reflex

- Posture and balance

36
Q

Sensory component of stretch reflex

A

Sensory = muscle spindle fibre

  • Detects stretch. i.e. length
  • Proprioception

Spindle is parallel to other muscle fibres
Ipsilateral spinal reflex
Monosynaptic

37
Q

What does a muscle spindle consist of

A
  • A spindle consists of 3-12 intrafusal fibres
38
Q

Purpose of gamma motor neurons

A

Gamma motor neurons increase sensitivity
- Drive contraction of edge of intrafusal fibres

Sensors from muscle spindle are:

  • Called type 1a and type 2
  • Wrap around the intrafusal fibres
  • Detect stretch (ie length) of central non-contracting region using stretch receptors

Spindle is like a thermostat that regulates the relationship between muscle length and muscle contractility.
ie the relationship between neural drive and force generation

39
Q

What does westphal’s sign indicate

A
  • Receptor damage
  • Femoral nerve damage
  • Peripheral nerve disease e.g. peripheral neuropathy
40
Q

What can upper motor neuron disease lead to

A
  • Can lead to hypertonia and spasticity
  • UMN inhibits normal descending inhibitory inout to spinal interneurons
  • The spindle reflex becomes over-sensitive(can attempt to contract muscle all the time)
41
Q

Purpose of a tendon reflex

A
  • Protects from overloading
  • Decreases muscle force –> dropping the load
  • Sensor firing –> decrease in contraction
42
Q

Tendon reflex path

A
  • Sensor to spinal cord
  • Interneuron to motor neuron
  • Motor neuron inhibited
  • Motor neuron to muscle
  • Neuron from golgi tendon organ fires
  • Motor neuron is inhibited
  • Muscle relaxes
  • Load is dropped
43
Q

What does a sensor consist of in the tendon reflex path

A 
Sensor = golgi tendon organ 
- Detects tension 
- In series with muscle 
- In tendon (near border with muscle) 
Disynaptic 
Ipsilateral spinal reflex

Year 2 - T3 Theme 2 (17 decks)

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