E-C Coupling and Skeletal Muscle Contraction

Question 1

How much of the body is made up of skeletal, smooth and cardiac muscle?

Answer 1

• ~40% is skeletal muscle in males, slightly less in females as they have more fat/adipose tissue
• ~1-% is smooth and cardiac muscle
• at the molecular level they all contract in the same way

Question 2

Skeletal muscle fibre

Answer 2

• a muscle cell
• relatively large, elongated and cylinder shaped
• can be entire length of muscle they comprise
• 10-100um in diameter and up to ~75 cm in length
• multiple nuclei
• abundance of mitochondria
• striated by a highly organised internal arrangement

Question 3

Myofibrils

Answer 3

• specialised contractile elements that extend the entire length of the muscle fibre
• muscle fibre can contain 100s to 1000s of myofibrils
• each myofibril consists of a regular arrangement of cytoskeletal elements (the thick and thin elements)
• parallel

Question 4

Thick elements

Answer 4

special assemblies of myosin

Question 5

Thin elements

Answer 5

special assemblies of actin

Question 6

Levels of organisation in a skeletal muscle

Answer 6

• whole skeletal muscle (organ)
• muscle fibre (single cell)
• myofibril (specialised intracellular structure)
• thick and thin filaments (cytoskeletal elements)
• myosin and actin (protein molecules)

Question 7

What are muscle fibres surrounded by?

Answer 7

connective tissue

Question 8

Muscles are attached to…

Answer 8

bones by a non-contractile tendon. These are organised into bundles of muscle fibres connected to connective tissue sheath.

Question 9

Dark myofibril bands

Answer 9

• A band
• contains thick filament
• overlaps with light filament
• arranged in a triangular array

Question 10

Light myofibril bands

Answer 10

• I band
• thin filament
• thick filaments don’t usually extend here
• must be kept in register
• line up parallel next to each-other
• arranged in a hexagonal array

Question 11

M line

Answer 11

• formed by structural proteins
• central
• keeps A bands together

Question 12

Z line

Answer 12

• keeps I bands together
• the area between two Z lines is called a sarcomere
• flat, cytoskeletal disc
• each sarcomere is about 2.5um in width

Question 13

H zone

Answer 13

• centre of A band

- occupied by thick filaments that the thin filaments don’t intrude into

Question 14

Neuromuscular Transmission

Answer 14

• skeletal muscles are stimulated to contract by release of ACh at the NMJ
• binding of ACh brings about membrane permeability changes in muscle fibre, resulting in an action potential (AP) that is conducted over the entire surface of the muscle cell membrane

Question 15

What is excitation-contraction coupling?

Answer 15

• E-CC
• how the muscle converts an electrical stimulus (action potential) into a mechanical response (contraction)
• APs cause release of calcium ions inside the muscle fibre in the immediate vicinity of the microfibrils, and these calcium ions then cause contraction

Question 16

Two important membranous structures that play an important role in E-CC

Answer 16

• transverse tubules

- sarcoplasmic reticulum

Question 17

During contraction…

Answer 17

cycles of cross-bridge interaction between actin and myosin brings about muscle contraction by means of the sliding filament mechanism

Question 18

How do APs spread to interior of the muscle fibre?

Answer 18

• transverse tubules
• the skeletal muscle fibre is so large that APs spreading along its surface cause almost no current flow deep within the fibre
• maximum muscle contraction requires the current to penetrate deeply into the fibre to the vicinity of seperate myofibrils
• this penetration is achieved by transmission of APs along T tubules
• these penetrate all the way through the fibre from one side to the other

Question 19

Release of calcium from the SR

Answer 19

• The SR is a modified endoplasmic reticulum that consists of a fine network of interconnected membrane enclosed compartments surrounding each myofibril like a mesh sleeve.
• The ends of each segment expand to form sack-like regions, the lateral sacs (terminal cisternae) which are separated from the adjacent T tubules by a slight gap.
• The lateral sacs store Ca2+. The spread of an AP down a T tubule triggers release of Ca2+ from the SR into the cytosol.
• Within the vesicular tubules of the SR is an excess of calcium ions in high concentration.
• Many of these calcium ions are released from each vesicle when an AP occurs in the adjacent T-tubule.

Question 20

Summary

Answer 20

• Action potential on surface of muscle firbre which dips into T-tubule system and activations the DHP receptor
• Physical coupling pulls the plug out of R receptor and allows it to release calcium
• When fibre repolarises, no more calcium is released and there is relaxation of the muscle
• Cytoplasmic reticulum special pump calcium ATPase (active transport)
• This uses ATP to provide energy to actively pump calcium against its concentration back into the cytoplasmic reticulum
• 10,000 V gradient
• Should be an excessive amount of energy
• Gradient of 3 ion concentrations
• Calcium binds to casequestrin reduces the energy required

Question 21

What next?

Answer 21

• Calcium is released into the cytosol from the lateral sacs through all the open Ca2+-release channels.
• This released Ca2+ exposes the binding sites on the actin molecules so they can link with the myosin cross bridges at their complementary binding sites.
• This is the start of the cross bridge cycle.

Question 22

What does the calcium pump do?

Answer 22

removes calcium ions from the cytoplasm after contraction

Question 23

What happens once Ca has been released from the SR?

Answer 23

• muscle contraction will continue as long as the calcium concentration remains high
• however, a continually active calcium pump (ATP dependent) located in the walls of the SR pumps Ca back into the SR
• this pump can concentrate the calcium ions ~10,000 fold inside the tubules

Question 24

Calsequestrin

Answer 24

a protein inside the SR that can bind up to 40-times more calcium

Question 25

Escitatory pulse of Ca

Answer 25

• Resting state [Ca2+]cytosol (= <10-7 M) is too little to elicit contraction.
• Conversely, full-excitation of the T-tubule/SR system causes release of Ca2+ to increase the [Ca2+]cytosol to 2 x 10-4 M (500-fold increase). This is about 10x the level required to cause maximum muscle contraction.
• Immediately thereafter, the calcium pump depletes [Ca2+]cytosol again.
• The total duration of this Ca2+ “pulse” in a skeletal muscle fibre is ~1/20 of a sec. (In cardiac muscle ~1/3 of a sec. – see next slide)
• During this pulse contraction occurs.
• If the contraction is to continue for longer periods, a series of calcium pulses must be initiated by a continuous series of repetitive APs.