Excitation-contraction coupling and muscle-fibre types

Question 1

How does electrical excitation by a neuron cause the muscle to contract?

Answer 1

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 )

Question 2

What is on the surface of muscle fiber

Answer 2

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.

Question 3

Excitation-contraction coupling

Answer 3

1- motor neuron action potential
2-Ca2+ enters voltage gated channel
3-Acetylcholine release
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.

Question 4

what is the role of the Dihydropyridine receptor?

Answer 4

• 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

Question 5

Dihydropyridine receptor is voltage regulated, what does that mean?

Answer 5

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.

Question 6

contraction process

Answer 6

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.

Question 7

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

Answer 7

plasma membrane
transverse tubules (T-tubules).
T-tubules
calcium

Question 8

Relaxation process

Answer 8

1. Ca2+-ATPase actively sequesters Ca2+ into sarcoplasmic reticulum
2. Ca2+ removal leads to covering of myosin binding sites by troponin, ceasing cross-bridge cycle.

Question 9

Why is there a latent period?

Answer 9

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.

Question 10

Why does it take so long for force generation to peak?

Answer 10

Contraction period –> Calcium binds to troponin –>reveals actin binding site, crossbridges form –>10-100 ms
Peak tension –> largest number of cross-bridges formed

Question 11

Why does force generated last for so long?

Answer 11

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

Question 12

What limits the maximum force generation?

Answer 12

1. 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
2. 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.

Question 13

Sliding filament model explains length-tension relationship

Answer 13

•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

Question 14

What about active tension?

Answer 14

• 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.

Question 15

Isotonic

Answer 15

– 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

Question 16

Isometric

Answer 16

– 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.

Question 17

What happens at the molecular level of cross-bridging cycle in isometric and isotonic?

Answer 17

cross-bridge cycling always occurs when action potentials reach the muscle fibres
If no lengthening occurs, cross-bridges simply rebind in the same place

Question 18

Concentric contraction

Answer 18

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

Question 19

Eccentric contraction

Answer 19

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

Question 20

What about walking down stairs – consider quadriceps muscle

Answer 20

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

Question 21

Types of skeletal muscle fiber

Defined based on:

Answer 21

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

Question 22

Three fiber types:

Answer 22

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.

Question 23

Twitch fibers come in three types:

Answer 23

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

Question 24

Type l and Type ll motor units

Answer 24

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

Question 25

fast-glycolytic fiber

Answer 25

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