Physiology of skeletal muscle contraction Flashcards
How troponin works
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
Total TnI
Marker for total muscle breakdown
Cardiac TnI
Marker for myocardial infarct
Cross bridge cycling
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
Cross bridge cycle reactions
Myosin releases actin
Myosin head cleaves ATP
Myosin binds actin
Power stroke
ATP, creatine phosphate and creatine phosphokinase
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
Creatine vs creatinine
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)
Two Ca2+ gradients
Extracellular vx cytosolic free Ca2+
SR vs cytosolic free Ca2+
Depolarisation leads to increase in Ca2+
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
Ryanodine receptor
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
Tetany: molecular basis
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
Two main types of muscle fibres
Slow twitch
- type 1- red- oxidative
- high myoglobin
- many mitochondria
Fast twitch
- type 2- white- nonoxidative
- lower myoglobin
- increase energy from glycolysis
Fibre types differ in
Aerobic vs anaerobic
Faster calcium re-uptake
Maximum tension produced
Fatigue resistance
Distribution of fibre types
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
3 types of muscle coordination
Motor units
- recruitment and size principle
Tetany
Fusion of myocytes into long myofibres
Definition of motor unit
A single alpha motor neuron and all muscle fibres it innervates
Motor units
Function as a single contractile unit of skeletal muscle
All muscle fibres in a single motor unit are of the same type
Motor units: variety
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
Isometric contraction
Generates a variable force while length of muscle remains unchanged
Isotonic contraction
Generates a constant force while the length of the muscle changes
Concentric force generation
Force during contraction- tossing ball into air
Eccentric force generation
Force during muscle elongation
Proprioception
Controls force generation based on length and stretch
Size principle
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
Lower motor neuron disease
Weakness
Muscle atrophy
Upper motor neurone disease
Spasticity
Hypertonia
Stretch reflex
Controls muscle length
Increases muscle force
Lack of patellar reflex= Westphal’s sign
Stretch reflex: patellar
Sensory= muscle spindle fibre
- detects strethc
- proprioception
Spindle is parallel to other muscle fibres
Ipsilateral spinal reflex
Monosynaptic
Muscle spindle
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
Sensors from muscle spindle
Called type 1a and type 2
Wrap around the intrafusal fibres
Detect stretch of central non-contracting region using stretch receptors
Absence of muscle spindle reflex
Westphal’s sign
Receptor damage
Femoral nerve damage
Peripheral nerve disease
- e.g. peripheral neuropathy
Muscle spindle reflex in upper motor neuron disease
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
Tendon reflex
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
Tendon reflex sensor
Golgi tendon organ
- detects tension
- in series with muscle
- in tendon (near border with muscle)
Disynaptic
Ipsilateral spinal reflex
