Physiology of skeletal muscle contraction

Question 1

How troponin works

Answer 1

4 Ca2+ bind to troponin C

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 to actin

• myosin break down ATP
• myosin pulls thin filaments

Question 2

Total TnI

Answer 2

Marker for total muscle breakdown

Question 3

Cardiac TnI

Answer 3

Marker for myocardial infarct

Question 4

Cross bridge cycling

Answer 4

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, mypsin heads are blocked from binding to actin by tropomyosin, which occupies the specific binding sites

Question 5

Cross bridge cycle reactions

Answer 5

Myosin releases actin

Myosin head cleaves ATP

Myosin binds actin

Power stroke

Question 6

ATP, creatine phosphate and creatine phosphokinase

Answer 6

Creatine found in muscle fibres

• phosphorylated to creatine phosphate
• how energy is stored in muscle

When cross bridge cycling hydrolyses ATP to ADP+ Pi, creatine phosphate donates a high energy phosphate to ADP restoring it to ATP
- ATP levels must be kept stable- buffering and regeneration

Reaction is catalysed in both directions by the enzyme creatine phosphokinase

Question 7

Creatine vs creatinine

Answer 7

Creatine is a small molecule that can accept high energy phosphate bonds from ATP

Creatine phosphate is the when phosphate has been added to it

Creatine phosphokinase is the enzyme that adds phosphate to creatine

• plasma marker of muscle destruction
• large molecule detected by antibodies

Creatine kinase is the same enzyme

Creatinine is a diagnostic marker of kidney function (breakdown product of creatine)

Question 8

Two Ca2+ gradients

Answer 8

Extracellular vx cytosolic free Ca2+

SR vs cytosolic free Ca2+

Question 9

Depolarisation leads to increase in Ca2+

Answer 9

ACH leads to depolarisation

Active nicotinic AChR leads to net inward current

Depolarisation spread via T-tubules

Local action potentials trigger Ca2+ efflux from terminal cisternae

• across membrane of SR
• into the fibre cytoplasm

Question 10

Ryanodine receptor

Answer 10

In SR membrane

Releases Ca2+

From SR

Triggered by voltage sensor on Ca2+ channel

Question 11

SERCA

Answer 11

In SR membrane

Pumps Ca2+ back into SR

Needs ATP

Question 12

Tetany: molecular basis

Answer 12

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

Question 13

Two main types of muscle fibres

Answer 13

Slow twitch

• type 1- red- oxidative
• high myoglobin
• many mitochondria

Fast twitch

• type 2- white- nonoxidative
• lower myoglobin
• increase energy from glycolysis

Question 14

Fibre types differ in

Answer 14

Aerobic vs anaerobic

Faster calcium re-uptake

Maximum tension produced

Fatigue resistance

Question 15

Distribution of fibre types

Answer 15

Muscles contain mixtures of fibre types, composition depends on muscle action

Soleus= 80% type 1 (slow), 20% type 2a

Vastus lateralis= mixture of type 1, 2a, 2x

Proportions depend on physical fitness

Question 16

3 types of muscle coordination

Answer 16

Motor units
- recruitment and size principle

Tetany

Fusion of myocytes into long myofibres

Question 17

Definition of motor unit

Answer 17

A single alpha motor neuron and all muscle fibres it innervates

Question 18

Motor units

Answer 18

Function as a single contractile unit of skeletal muscle

All muscle fibres in a single motor unit are of the same type

Question 19

Motor units: variety

Answer 19

Large muscles responsible for powerful gross contractions, as 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

Different sorts of motor units in a single muscle

Question 20

Isometric contraction

Answer 20

Generates a variable force while length of muscle remains unchanged

Question 21

Isotonic contraction

Answer 21

Generates a constant force while the length of the muscle changes

Question 22

Concentric force generation

Answer 22

Force during contraction- tossing ball into air

Question 23

Eccentric force generation

Answer 23

Force during muscle elongation

Question 24

Proprioception

Answer 24

Controls force generation based on length and stretch

Question 25

Size principle

Answer 25

As the initial isometric contraction occurs: - more and more motor units are recruited - starts with smaller ones and progressively adds larger ones Allows fine gradation of force for small movements

Question 26

Lower motor neuron disease

Answer 26

Weakness Muscle atrophy

Question 27

Upper motor neurone disease

Answer 27

Spasticity Hypertonia

Question 28

Stretch reflex

Answer 28

Controls muscle length Increases muscle force Lack of patellar reflex= Westphal's sign

Question 29

Stretch reflex: patellar

Answer 29

Sensory= muscle spindle fibre - detects strethc - proprioception Spindle is parallel to other muscle fibres Ipsilateral spinal reflex Monosynaptic

Question 30

Muscle spindle

Answer 30

Spindle consists of 3-12 intrafusal fibres Gamma motor neurons increase sensitivity - drive contraction of edge of intrafusal fibres Spindle is like a thermostat that regulates the relationship between muscle length and muscle contractility

Question 31

Sensors from muscle spindle

Answer 31

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

Question 32

Absence of muscle spindle reflex

Answer 32

Westphal's sign Receptor damage Femoral nerve damage Peripheral nerve disease - e.g. peripheral neuropathy

Question 33

Muscle spindle reflex in upper motor neuron disease

Answer 33

Can lead to hypertonia and spasticity UMN inhibits normal descending inhibitory input to spinal interneurons Spindle reflex becomes over sensitive Can attempt to contract muscle all the time

Question 34

Tendon reflex

Answer 34

Protects from overloading Decreases muscle force -> dropping the load Sensor firing -> decrease contraction - sensor to spinal cord - interneuron to motor neuron - motor neuron inhibited - motor neuron to muscle

Question 35

Tendon reflex sensor

Answer 35

Golgi tendon organ - detects tension - in series with muscle - in tendon (near border with muscle) Disynaptic Ipsilateral spinal reflex