How does electrical excitation by a neuron cause the muscle to contract?
Excitation : stimulation of muscle fibres by action potential (an electrical event -> transformed into a chemical event ->electrical event ->into a mechanical event (which is our contraction)
Contraction : interaction between actin and myosin (mechanical event )
What is on the surface of muscle fiber
Entire surface of muscle fibre is electrically active (i.e. Contains voltage-activated channels). However, there are specialised neuromuscular junctions – contact point between nerve and muscle fibres.
1- motor neuron action potential
2-Ca2+ enters voltage gated channel
4-Acetylcholine binding opens ion channels
5- Na+ entry
6- local current between depolarized end plate and adjacent muscle plasma membrane
7- muscle fiber action potential initiation
8- propagated action potential in muscle plasma membrane
9- Acetylcholine degradation
Note that to prevent ongoing AP and contraction, acetylcholine-esterase breaks down Ach.
what is the role of the Dihydropyridine receptor?
- Dihydropyridine receptor is a voltage-gated Ca2+ channel – it opens in response to AP
- DHP receptor and ryanodine receptor are physically coupled Ca2+ channels
- AP increases cytosolic calcium levels because Ca2+ is release from the Sarcoplasmic Reticulum
- The high intracellular Ca2+ triggers muscle contractions
- Ca2+-ATPases pump Ca2+ ions from cytosol back into the SR
Dihydropyridine receptor is voltage regulated, what does that mean?
It means it changes shape when the voltage changes.
That means that when the AP comes, there’s a release of ACH –> influx of NA2+ –> then there’s a spread of action potential to the t-tubules
When the DHP receptors change shape they connect to the Ryanodine receptor and open it like a treasure box and then inside it spills out Ca2+ from the SR
Remember – cytosolic, or intracellular Ca2+ concentration is normally kept very low.
What ions are DHP and ryanodine receptors permeable to? Ca2+
Action potential propagates along surface of plasma membrane (grey) and down into transverse tubules.
1- Myosin head is initially unbound, but “energised”
2- Actin binding site is blocked by tropomyosin
3- Ca2+ binds to troponin, moving tropomyosin
4- Myosin cross-bridges bind to actin
5- power stroke: myosin head rotates
6-ATP binding to myosin breaks A-M linkage
7- Bound ATP is split, re-energising myosin head.
Action potential propagates along the muscle fibre……… and down into ……….
……….. are electrically continuous with surface of plasma membrane.
The sarcoplasmic reticulum is a massive intracellular …… store
transverse tubules (T-tubules).
- Ca2+-ATPase actively sequesters Ca2+ into sarcoplasmic reticulum
- Ca2+ removal leads to covering of myosin binding sites by troponin, ceasing cross-bridge cycle.
Why is there a latent period?
Latent period–> the time it takes for the AP to travel to the muscle, Calcium ions released from the SR into the sarcoplasm –> (about 2-5 ms). Also, taking up slack.
Why does it take so long for force generation to peak?
Contraction period –> Calcium binds to troponin –>reveals actin binding site, crossbridges form –>10-100 ms
Peak tension –> largest number of cross-bridges formed
Why does force generated last for so long?
Complete Ca2+ sequestration takes some time
Relaxation –> calcium is transported by ATP + calcium atpase back to the SR, troponin moves tropomyosin to cover the actin binding sites –> tension decreases over time up to 100ms
What limits the maximum force generation?
- It takes time for cross-bridge binding to occur during this time the calcium can be sequestered back to SR from the intracellular space
a. the rate of action potential and how they arrive relative to the build of force from pervious action potential
- Passive muscle tension from titin filaments
Titin’s primary functions are to stabilize the thick filament, center it between the thin filaments, prevent overstretching of the sarcomere, and to recoil the sarcomere like a spring after it is stretched.
Sliding filament model explains length-tension relationship
•Optimal length – dependent on optimal overlap of actin and myosin
•Maximum length – no overlap of actin/myosin
•Minimum length – limited by
(1) thin-filament overlap;
(2) overlap of thick-filaments and Z-discs
What about active tension?
- There is an optimal resting length for generating tension – dependent on overlap of actin and myosin.
- Cannot shorten more than ~60% - at this point or generate tension beyond ~175% of optimal length.
- Partial explanation – sliding filament model.
- When very short – get overlapping of thin filaments. Z-lines collide with end of thick filament.
– muscle changes length while maintaining constant tension
- constant number of myosin cross bridges happening over time
they rebind at different places of actin filaments pulling the actin filaments
– muscle develops tension without changing length.
in isometric, rotation during power stroke (i.e. When cross-bridge changes angle) is absorbed by the cross-bridge. Force is maintained.
What happens at the molecular level of cross-bridging cycle in isometric and isotonic?
cross-bridge cycling always occurs when action potentials reach the muscle fibres
If no lengthening occurs, cross-bridges simply rebind in the same place
Bicep muscle shortening while contraction
should be intuitive – you have a load, you contract the muscle and the muscle shortens. E.g. Rising phase of a bicep curl.
However, when you lower a weight in a controlled manner, this is an eccentric contraction. Still stimulating muscle to maintain tension, but lengthening it .
Concentric muscle contraction
After power stroke (B->C) myosin head progressively binds further along actin filament, leading to shortening. binding at site 1 then 2
Bicep muscle lengthening while contraction
– potentially more damaging, but also good in muscle training.
External force applied to muscle means it lengthens even as power strokes occur
What about walking down stairs – consider quadriceps muscle
Stepping down – contracting quadriceps controls rate of knee flexion against gravity => Still have tension generation in muscle, but it must now lengthen in order to take a step down => eccentric contraction with each step
Types of skeletal muscle fiber
Defined based on:
1) Maximum shortening velocity
Type I – Slow – low ATPase activity
Type II - Fast – high ATPase activity
ATPase activity affects maximal rate of cross-bridge cycling
2) ATP pathway (enzymatic machinery)
a.Oxidative - depend on oxygen => numerous mitochondria, good blood supply, lots of myoglobin, red colour
b.glycolytic – large glycogen stores
generally thicker => greater tension development white colour
Three fiber types:
1a – slow oxidative
2a – fast oxidative 2b – fast glycolytic
The muscle fibers in a single motor unit are of the same type.
Different muscles contain different proportions of the three fiber types.
Twitch fibers come in three types:
Type I - Slow-twitch oxidative Use ATP at a relatively low rate.
Type IIa - Fast-twitch oxidative - Rapid, sustained movements. Many mitochondria produce lots of ATP to sustain this movement
Type IIb - Fast-twitch glycolytic - Few mitochondria, depend a lot on glycolysis to produce ATP
Slow-glycolytic fibers do not exist
Type l and Type ll motor units
Type I fibers have motor units that:
- have smaller cell bodies and smaller diameter axons
Produce steady, low-frequency activity (10-20 Hz)
Type II fibers have motor units that:
- Have larger cell bodies and larger diameter axons
produce occasional, high frequency bursts (30-60 Hz
motor units comprising fast-glycolytic fibers, which are the most rapidly fatiguing, also have the largest diameter and therefore produce the most force. Due to the large number of muscle fibers, they are innervated by alpha motor neurons with the largest cell bodies =>need the highest rates of neuronal drive to activate them.
- Oxidative/glycolytic map onto fatigue-resistant/fatiguable