Muscle Physiology Flashcards
Give a brief description of skeletal muscle structure:
Skeletal muscles are made up of elongated cylinders (10-100um in diameter and up to 75cm long) that contain myofibrils/contractile elements
Force is developed in muscles due to the interaction between ______ and ________.
Actin
Myosin
What are some defining characteristics of skeletal muscle cells?
Multinucleated cells
Striations
Nuclei pushed out to the sides
Actin is a relatively _______ protein that forms the __________. It has 2 associated proteins: ___________ and _________
Relatively Small
Forms Filaments
Tropomyosin and Troponin
What is the role of Tropomyosin?
- Helps stabilise the actin filaments
- Covers the myosin binding sites .’. prevents interaction in a resting fibre
What is the role of Troponin?
Controls contractile activation
Myosin is a relatively _______ protein that consists of 2 __________ and 2 ________.
Large
2 Heavy chains
2 Light chains
The 2 heavy chains in myosin form a _____________ region and the ___ termini form ______________________.
Helical and coiled region
NH3 termini
2 globular heads
The 2 light chains in myosin form a _________________ region. These combine to produce ________________.
Flexible tail region
The thick filament
What is isometric contraction?
Muscle develops tension at a constant length
What is isotonic contraction?
The muscle shortens but the load remains constant
Outline the Cross-Bridge Cycle:
- ATP binds to myosin heads = release from actin
- Myosin heads are displaced and attach further up the filament. Whilst bound ATP is hydrolysed to for ADP and Pi
- When myosin heads bind again to actin Pi is released triggering a power stroke. ADP is lost during the power stroke
- Myosin heads are reattached to its original configuration
Muscle contraction is triggered by a rise in _____ from around ________ μmol/L to _______ μmol/L
Ca
0.05 - 0.1 μmol/L
1 - 10 μmol/L
What are the 3 subunits of troponin?
Troponin C - Ca binding site, binds 4 Ca in skeletal muscle
Troponin T - Tropomyosin binding site
Troponin I - Inhibitory site
Explain how Ca causes contraction:
- 4 Ca ions bind to Troponin C
- Tropnonin C changes shape and moves tropomyosin to expose the myosin binding site
- Cross-bridges can now form
Explain the events of excitation-contraction coupling in skeletal muscle:
- AP travels along sarcolemma and down the T-Tubule system
- AP depolarises voltage sensors in the T-Tubule membrane
- Because they are mechanically connected voltage sensors then cause the opening of Ca release channels on the Sarcoplasmic reticulum
- Large flux of Ca released into the myoplasm
- Ca diffuses to the contractile units and causes contraction
- After stimulation ceases Ca is pumped back into the SR and contraction ceases
What is a twitch response?
A single action potential causes a cross bridge cycle that lasts 5-10ms and then rapidly decays.
Lots of Ca release but small contraction.
Why does a twitch response result in a small contraction?
Because the AP ceases so does Ca release. Ca is that rapidly pumped back into the SR.
What is twitch summation?
When another AP is triggered after the the first the response will summate due to the reopening of Ca channels, this means more Ca enters the myoplasm and can cause contraction.
What is Tetanus?
Tetanus is sustained muscle contraction. It is due to high frequency stimulation causing constant release of Ca which keeps Ca levels high. Summation occurs and is sufficient to prevent relaxation between stimulations.
How does Increasing muscle length affect muscle tension?
- Increases passive tension
- Increases active tension until optimal length
- Decreases active tension after optimal length
When compared to skeletal muscle cells cardiac cells:
- Are considerably shorter
- Have Branched processes
- Have a less developed SR
- Have gap junctions, allowing electrical communication between cells
- Have a different mechanism of excitation contraction coupling
What are the 3 phases of the Cardiac Action Potential?
Depolarisation phase (Na influx) Plateau phase (Ca influx) Repolarisation phase (K efflux)
What causes the action potential delay at the AV node?
Fibres in the AV node have small diameters resulting in slower movement of potential
Explain the process of excitation-contraction coupling in cardiac muscle:
- Depolarisation of the Sarcolemma opens Ca channels leading to a long lasting Ca influx
- Inflowing Ca binds to sites on the Ca release channels of the SR and causes more Ca release (Ca-induced Ca Release)
- Released Ca binds to cardiac troponin (only 1 binding site for Ca) and contraction occurs.
What is a motor unit?
1 motor neuron and the muscle fibres it innervates
How do we control the level of force exerted by our muscles so precisely?
By controlling the number of motor units that are activated
What are the 3 main types of motor units?
S - Slow contracting and fatigue resistant
FR - Fast contracting and fatigue resistant
FF - Fast contracting and fast fatigue
The more power required the _____ motor units will be recruited
More motor units will be recruited
In what order are motor units recruited?
S –> FR –> FInt –> FF
What are the different types of muscle fibres?
Slow:
- Type I (aka Red): slow and oxidative
Fast:
- Type IIa: Fast, oxidative and glycolytic
- Type IIb (aka White): Fast, glycolytic
What is the difference between the stimulation of Slow and Fast twitch fibres?
Slow Twitch = Continuous nerve impulses of low frequency
Fast Twitch = Intermittent nerve impulses of high frequency
Describe smooth muscle cells
- Small elongated spindle/fusiform shaped
- 3-5μm wide and 200-500μm long
- Single nucleus
- Involuntary
- No striations
How are smooth muscle cells innervated?
- Can be activated spontaneously or by nervous or hormonal stimulation
- Neuromuscular junction is not as highly developed as in striated muscle
- Fine nerve bundles wind through the muscle and display varicosities (swelling)
- Varicosities release neurotransmitter onto cells near the nerve
What are the 2 types of smooth muscle?
Tonic smooth muscle and Phasic smooth muscle
What are the characteristics of Tonic Smooth Muscle?
- Maintain tone effectively
- Have slower shortening velocities
- Display no AP or electrical activity
e. g. Aorta, Trachea, Oesophageal Sphincter
What are the characteristics of Phasic Smooth Muscle?
- Maintain tone poorly
- Have relatively fast shortening velocities
- Capable of display AP or regenerative electrical activity
e. g. Taenia coli of intestine, antrum of the stomach
What is tone?
The ongoing maintenance of a baseline of contractile activity
Many phasic smooth muscle cells are connected electrically by _______________.
Gap Junctions
What are the advantages of having gap junctions in muscle cells?
- Allow electronic spread of current from cell to cell (AP in one cell triggers AP in neighbouring cells)
- Electrical coupling allows the muscle to move as a single unit
Smooth Muscle cells without gap junctions and electrical couplings are called _________ and are usually _______ smooth muscle.
Multi-unit
Tonic smooth muscle
What are the features of Multi-Unit smooth muscle?
- Not spontaneously active
- Have a stable resting membrane potential
- Their tone is largely under control of extrinsic nerves
- Innervation is well developed
e. g. trachea, arteriole smooth muscle
What are the features of Unitary smooth muscle?
- Spontaneously active
- Have an unstable resting membrane potential
- Their tone is largely independent of extrinsic nerves
- Innervation is not well developed
e. g. Duodenum, seminiferous tubule smooth muscle
What causes APs in smooth muscle cells?
The rising phase and plateau phase (if present) is cause by inward Ca current via voltage-dependent and slowly inactivating Ca channels
K channels open to provide outward current to return the membrane potential towards the equillibrium
How are the contractile proteins organised in smooth muscle?
Thin filaments:
- Similar to skeletal muscle except it doesn’t contain troponin
Thick filaments:
- Different type of myosin
- 2 heavy chains form the neck and 2 globular heads
- 2 kinds of light chain attach to myosin heads, 1 is essential for ATPase activity and the other has regulatory functions
Explain the arrangement of the contractile proteins in a smooth muscle cell
- Filament bundles are orientated obliquely
- Actin is joint together by dense bodies (like mini Z-lines)
- Actin filaments can slide in opposite directions on either side of the filament (allows greater shortening)
- Actin filaments can slide over the entire length of the myosin .’. myofilament overlap is constant during shortening so maximal force can be developed over a wide range of lengths
What is the mechanism that results in increased calcium in phasic smooth muscle cells?
Opening of voltage gated Ca channels in response to electrical stimulation
What is the mechanism that results in increased calcium in tonic smooth muscle cells?
- Release of Ca from SR
- Contracts in the absence of external Ca levels
- SR is much more abundant than in phasic smooth muscle
What is the Phospholipase C-IP3 pathway?
The major pathway causing Ca release from the SR in smooth muscle
Outline the Phospholipase C-IP3 pathway?
- Receptor is occupied by Ach or Adr which acts via a G-protein to activate the enzyme Phospholipase C
- Phospholipase C converts the membrane lipid PIP2 into IP3 and DAG
- IP3 diffuses to the SR and binds to ligand gated Ca channels .’. Ca is released
How does Ca cause contraction in smooth muscle?
- Ca interacts with calmodulin
- The Ca-Calmodulin complex activates an enzyme called myosin light chain kinase (MLCK) which phosphorylates the myosin light chain on the myosin molecule near its head
- Only Phosphorylated myosin is able to interact with actin and hydrolyse ATP
Phosphorylation of myosin increase ATPase activity at least 100 fold
How do smooth muscle cells relax?
- Myosin Phosphatase dephosphorylates the myosin and induces relaxation
- The action of Myosin Phosphatase is only effective when Ca is removed and phosphorylation by MLCK ceases
