Muscle structure and contraction

Muscle Contraction Striated muscle is made from many fibres laid down in parallel. The muscle fibres are made from several cells that share a common cell membrane: the cytoplasm (sarcoplasm) contains many nuclei technically this is a syncitium (cells fused) The multinucleate muscle fibre is surrounded by a membrane called the sarcolemma it has infoldings called T-tubules cytoplasm has a large amount of smooth ER stores Ca2+ ions that are needed for contraction the SER is called sarcoplasmic reticulum 2

Striated muscle is made from many fibres laid down in parallel 3

The muscle fibres are made up of two types of protein: thick filaments of myosin with a ‘head’ projecting from it thinner actin filaments made up of repeating protein units tropomyosin and troponin are associated with the actin and are important for contraction 4

Bundles of myosin molecules make up the thick filaments. Myosin molecules consist of a long filament with a ‘head’ projecting from it. Myosin molecules are bundled together to produce thick bundles with equal numbers of myosin heads in each half. Bundles of myosin molecules make up the thick filaments Myosin head M-line Long myosin molecule 5

Actin consists of many globular protein units linked together into long chains. Two of these actin chains are twisted together with a tropomyosin molecule lying in the groove between them. At intervals, troponin molecules bind to the actin, covering the binding sites of the myosin heads. Tropomyosin Troponin Globular protein that makes up the actin chain Actin chain 6

Each muscle fibre is made from many myofibrils that are composed of thick myosin molecules and thin actin molecules. The regular arrangement of these molecules produces a banding pattern typical of voluntary muscle. This can be seen with the light microscope and electron microscope. 7

Z-line sarcomere H-band I-band A-band 9

The banded regions are given names or letters. A-bands: are the broad dark bands made from myosin they have an indistinct M-line (not labelled on the diagram) running down the centre of the band I-bands: are paler and not as broad have a dark Z-line running down their middle made from actin Sarcomere: the section between two Z-lines in voluntary muscle these sarcomeres are lined up give them a striped appearance 10

The banding pattern is clearly visible in electron micrographs of striated muscle. (Louisa Howard, public domain image) A-band Sarcomere Z-line I-band H-band M-line 11

During muscle contraction (details later), the actin filaments are pulled across the myosin filaments, towards the middle. Consequently: the I-bands and H-bands get smaller the A-band remains the same In the relaxed state, the sarcomere is 2.5 µm compared with 2.0 µm when contracted. 13

Z-line sarcomere Muscle relaxed: Muscle contracted: 14

Relaxed state Contracted state Length of sarcomere H-band width Complete the table to compare muscle when relaxed and contracted. Relaxed state Contracted state Length of sarcomere H-band width I-band width A-band width 15

Relaxed state Contracted state Length of sarcomere wider 2.5 µm Complete the table to compare muscle when relaxed and contracted. Relaxed state Contracted state Length of sarcomere wider 2.5 µm narrower 2.0 µm H-band width I-band width A-band width unchanged 16

The myosin head acts as an ATPase and hydrolyses the ATP When the muscle is stimulated, Ca2+ ions are released from the sarcoplasmic reticulum Ca2+ ions bind to troponin results in the myosin binding sites on the actin being uncovered The binding of the myosin head to the actin filament causes the head to bend pulls the actin over the myosin in the ‘power stroke’ bending of the myosin head releases ADP and Pi allows fresh ATP to bind The myosin head acts as an ATPase and hydrolyses the ATP breaks the bonds between the myosin head and actin allows the myosin head to return to its original shape then able to bind to other exposed binding sites and the cycle of contraction continues 17

Usually the myosin binding sites on the actin filaments are covered by the tropomyosin and troponin, so preventing binding of the myosin heads. ADP + Pi Actin filaments with binding sites covered Myosin head not bound When stimulated, Ca2+ ions are released from SER. This binds to the troponin, exposing the binding site which allows the myosin head to crosslink with the actin filament. Actin filaments with exposed binding sites Myosin head binds ADP + Pi The myosin head tilts (ca. 45o), moving the actin filament along by about 10 nm. This is the so-called power stroke. The change in shape causes the ADP and Pi to be released from the myosin head. ADP + Pi Actin filaments are pulled across the myosin 18

Fresh ATP binds to the myosin head and is hydrolysed to ADP + Pi Fresh ATP binds to the myosin head and is hydrolysed to ADP + Pi. The energy released by the hydrolysis allows the actin and myosin to separate. ATP ATP binds to myosin and brings about separation of the myosin head The detached myosin head flips back to the original position and is ready for another cycle to begin. Actin filaments with exposed binding sites, so cycle can begin again ADP + Pi 19

Q. What is the role of the ATP? Q. The troponin and tropomyosin normally block the myosin binding sites on actin. What is the role of the Ca2+ ions released from the sarcoplasmic reticulum? The Ca2+ ions bind to the troponin which then displaces the tropomyosin and so exposes the binding site on the actin.  Q. What is the role of the ATP? When it binds to the myosin head, it is hydrolysed. Release of energy allows separation of the myosin from the actin and the resetting of the head in its pre-power stroke position. 20

Role and Supply of ATP to Muscle ATP is required to: break the cross bridge or links between the myosin heads and actin reset the myosin head in its pre-power stroke form so that it can bring about further muscle contraction There is actually very little ATP present in the muscle fibres only enough for a few seconds contraction it must be resupplied if contraction is to continue This is achieved by: respiration – aerobic and anaerobic resupply from creatine phosphate reserves 21

Aerobic Respiration The sarcoplasm contains many mitochondria that complete the link reaction, Krebs cycle and oxidative phosphorylation. Respiration rates are high in active muscle and the supply of O2 must be maintained if aerobic respiration is to continue. Q. How do the following help to maintain O2 supply? Presence of myoglobin in muscle  High levels of CO2 in active muscle 22

myoglobin is respiratory pigment with a high affinity for O2 saturates at low pp O2 only gives it up at very low O2 i.e. when respiratory demands are greatest High levels of CO2 in active muscle: elevated CO2 causes the Bohr effect reduces haemoglobin’s affinity for O2 shifts O2 dissociation curve to the right makes more O2 available at times of high demand 23

Anaerobic Respiration Under anaerobic conditions, pyruvate can be diverted into the lactate pathway which ensures the resupply of NAD so that glycolysis and limited ATP production can continue. Unfortunately this cannot continue indefinitely and only relatively small amounts of ATP are produced. Q. Why is it not possible for anaerobic respiration to continue indefinitely? Q. How much ATP is produced per molecule of glucose under anaerobic compared to aerobic conditions? Suggest a reason for this. 24

Anaerobic respiration cannot continue indefinitely because lactate is toxic Limited ATP production aerobic respiration produces 32–38 ATP per glucose fully oxidised anaerobic respiration only produces 2 ATP glucose is not fully oxidised much energy still remains in the lactate 25

Regeneration of ATP in Muscle Creatine phosphate is a high energy compound. It can be used to regenerate ATP that has been used by the muscle. There is enough present in muscle for 2–4 seconds worth of contraction. ADP + CP  ATP + C The creatine phosphate can be made when aerobic respiration is taking place. 26