5. Physiology of muscle contraction Flashcards

1
Q

How does troponin unmask the myosin binding site on actin?

A

4 Ca2+ bind to troponin C (C = calcium binding),
In heart TnC only binds to 3 Ca2+ ions
TnC changes conformation

conformational change in TnC “shuts off” TnI
tropomyosin-troponin leaves F-actin groove
unmasks the myosin binding site on actin

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2
Q

What happens after actin’s myosin binding site is exposed?

A

next myosin heads make cross bridges (cycling) to actin
Myosin breaks down ATP
Myosin pulls thin filaments

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3
Q

What is TnI a marker for?

A

Total TnI = marker for total muscle breakdown

Cardiac TnI = marker for myocardial infarct

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4
Q

What is cross bridge cycling?

A

Molecular cycle of actin-myosin interaction

Mechanism of Contraction at Molecular level

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5
Q

What does contraction depend on?

A

contraction depends on binding of myosin heads to thin filaments (actin) at specific binding sites

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6
Q

What stops contraction when the sarcomere is at rest?

A

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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7
Q

Force generation vs sarcomere length

A

Increasing overlap thin and thick filaments -> increased force UP TO the optimal length

Greatest force generation occurs when sarcomere is at optimal length

When sarcomere is really small, everything overlaps so get no force at all
BUT if stretch sarcomere really far, then myosin heads don’t overlap with any actin so can’t generate any force

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8
Q

Cross bridge cycle reactions

A
  1. Myosin releases actin
  2. Myosin head cleaves ATP
  3. Myosin binds actin
  4. Power stroke
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9
Q

Creatine

A

creatine found in muscle fibres
phosphorylated to creatine phosphate

Stored in muscle as creatine phosphate

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10
Q

What role does creatine have in cross bridge cycling?

A

keeps ATP levels stable (buffering and regenerating it)

when ATP is hydrolysed to ADP and Pi, creatine phosphate donates a high energy phosphate to ADP, restoring it to ATP

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11
Q

What enzymes catalyse ATP to ADP + Pi with creatine phosphate?

A

the reaction is catalysed in both directions by the enzyme creatine phosphokinase (a/k/a CK, CPK)

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12
Q

Is creatinine and creatine the same?

A

No!
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 the 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 (above). They are the same thing.
Creatinine is a diagnostic marker of kidney function. It is a breakdown product of creatine.

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13
Q

What triggers contraction?

A

Calcium triggers contraction

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14
Q

Calcium gradients in 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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15
Q

What does depolarisation lead to?

A

Increase in Ca2+

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16
Q

Depolarisation

A

ACh -> Depolarisation

Active Nicotinic AChR -> net inward current

depolarisation spreads 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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17
Q

Excitation contraction (EC) coupling

A

the molecular mechanism for how the depolarisation of the plasma membrane leads to the release of Ca2+ into the cytoplasm followed by contraction.

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18
Q

Ryanodine receptor (RyR) aka Ca2+ release channel

A

In SR membrane
Releases Ca2+
From SR
Triggered by voltage sensor on Ca2+ channel

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19
Q

SERCA

A

In SR membrane
Pumps Ca2+ Back into SR
Needs ATP

20
Q

What is the molecular basis of tetany?

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

21
Q

What are muscle fibres divided into?

A

Slow twitch (type I, red)

Fast twitch (type II, white)

22
Q

Slow twitch fibres

A

oxidative, small diameter

high myoglobin, many mitochondria

23
Q

Fast twitch fibres

A

nonoxidative, wide diameter

lower myoglobin, more energy from glycolysis

24
Q

How do fibre types differ?

A

aerobic (slow) vs anaerobic

faster calcium re-uptake (fast)

maximum tension produced (fast)

fatigue resistance (slow)

25
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

26
Q

Proportions of fibre types depend on what?

A
proportions depend on physical fitness:
inactive
moderately active
endurance athlete
anaerobic athlete
27
Q

Types of coordination of muscle contraction

A

3 types of co-ordination

Motor Units
Recruitment & size principle

Tetany

Fusion of myocytes into long myofibres

28
Q

Motor units

A

Definition:
A single alpha motor neuron and all muscle fibres it innervates.

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).

29
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

30
Q

What determines type of muscle fibre?

A

type and function of the lower motor neuron determines the muscle fibre

31
Q

Contraction: force generation

A

isometric – generates a variable force while length of muscle remains unchanged.
“Iso” = same, “metric” = length

isotonic – generates a constant force while the length of the muscle changes
“tonic” = tone = tension/force

32
Q

What types of force generation are used when picking up a drinking glass?

A

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

33
Q

Types of muscular force generation

A

Muscle contraction ≠ (necessarily) muscle shortening

Concentric – force during contraction – tossing a ball into air

Eccentric (negatives) – force during muscle elongation
e.g. 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 gen. based on length and stretch

34
Q

Size principle

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

35
Q

Upper vs lower motor neuron disease

A

Lower motor neuron disease
Weakness
Muscle atrophy

Upper motor neurone disease
Spasticity, hypertonia

36
Q

Stretch reflex

A

Controls Muscle Length

Increases Muscle Force

Lack of patellar reflex = Westphal’s sign

37
Q

What are intrafusal and extrafusal fibres?

A

Can shorten muscle when it is too long for current neural drive

Sensory = Intrafusal fibres (inside sheath)

Contraction: extrafusal fibres

38
Q

An example of stretch reflex?

A

Patellar reflex

function: posture and balance

39
Q

Stretch reflex: patellar

A

Sensory = Muscle Spindle Fibre
Detects Stretch
i.e. Length (NOT FORCE)
Proprioception

Spindle is Parallel to other muscle fibres

Ipsilateral Spinal reflex

Monosynaptic

40
Q

Muscle spindle

A

A spindle consists of 3-12 intrafusal fibres
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

41
Q

Absence of muscle spindle reflex

A
Absence of this reflex = Westphal’s Sign
Receptor damage
Femoral nerve damage
Peripheral nerve disease 
e.g. Peripheral Neuropathy
42
Q

What can happen in upper motor neurone disease?

A

In upper motor neuron disease
Can lead to hypertonia and spasticity
UMN inhibits normal descending inhibitory input to spinal interneurons
The spindle reflex becomes over-sensitive
Can attempt to contract muscle all the time

43
Q

Tendon reflex

A

Protects from overloading

Decreases Muscle Force -> dropping the load
Sensor firing -> decreased contraction

44
Q

Tendon reflex pathway

A

Sensor to Spinal Cord

Interneuron to motor neuron

Motor neuron inhibited

Motor neuron to muscle

45
Q

Tendon reflex organ

A
Sensor = Golgi Tendon Organ
Detects Tension
In series with muscle
In tendon
Near border with muscle
46
Q

What type of reflex is the tendon reflex?

A

Disynaptic

Ipsilateral Spinal reflex