Medical Science - MUSCULAR-SKELETAL SYSTEM

• support soft tissues
• provide sites of attachment for skeletal muscles
• movement and posture - work with skeletal muscles
• protection of internal tissue and vital organs
• storage of minerals - Ca2+ and P most important

In long bones growth occurs at the epiphyseal plate.

• growth is initiated in the proliferation zone of cartilage where new cartilage is produced forming a layer and increasing the length of the bone. 
• old cartilage is ossified (made rigid and inflexible) forming new bone.

most bone growth occurs in the direction of maximum stress.

Oppositional growth - increase in diamter

• oseoclasts start breaking down/reabsorbing bone in the the hollow of the bone
• osteoblasts build up bone on the outside of the bone.

• A henatoma (blod clot) forms
• collagen fibres begin to connect the pieces of bone and pulls them together.
• osteoblasts create a spongy bone with trabeculae 
• new compact bone is formed, osteoclasts reabsorb the spongy bone and a new medullary cavity is formed.

• [Ca2+] too high : nerves become unresponsive and calcium deposits build up.
• [Ca2+] too low: nerves become hyper excitable where very small stimuli cause huge excitability.

Concentration monitored by parathyroid hormone, PTH, -> low [ca2+] = high [PTH]. A high level of PTH causes:

• increased number and activity of osteoclasts
• reduces loss of Ca2+ in the urine
• increases formation of Calcitrol in the kidney which promotes the uptake of Ca2+ in the gut. 

• Muscle is made of many fasicles. 
• Fasicles are made of muscle fibres arranged in bundles to form syncytiums. 
• Muscle fibres are formed by several cells fusing together. They are multinucleated. It contains multiple myofibrils running in parallel. 
• Myofibrils are made of actin and myosin filaments. The repeating unit for this is called a sarcomere.

Titin acts like a spring and contributes to the passive elastic properties of the muscle.
Nebulin is involved in length regulation of the thin filaments.

Muscle fibres contain myofibres as the active element.

• sarcolemma- a membrane that separates the cell from the extracellular space
• sarcoplasm- equivalent of a cytoplasm
• sarcoplasmic recticulum - stores and controls the release of Ca2+.
• tranverse, T tubules - form an extension of the sarcolemma and run deep into the tissue to establish a close proximity between functional subunits.
• myoglobin - carries oxygen around the inside of the muscle to where it is needed.
• mitochondria- produce ATP 

• Myosin heads split ATP and become energised and reorientate themselves. 
• The myosin binds to actin in the presence of Ca2+. A crossbridge is formed and PO4 is released.
• The myosin heads swivel sliding the actin towards the m line. ADP is released.
• Myosin remains attached to the actin until it binds to a new molecule of ATP when it detatches.

When the sarcolemma and T tubules are depolarised, Ca2+ channels in the sarcoplasmic reticulum are opened increasing the concentration of calcium in the sarcoplasm. The calcium binds to the Toponin causing it to move and expose the Myosin binding site on the Actin filaments. The Ca2+ is actively pumped back into the sarcoplasmic recticulum.

The higher the activation frequency, the longer it takes for the calcuim to be removed so more myosin binding sites become available and tension builds up - unfused tetanus. Beyond a certain activation threshold all binding sites become available for cross bridges -  fused tetanus.

A chemical synapse between a motor neuron and a muscle fibre. when the signal is sent to the muscle it causes a contraction.

• An action potential arrives at the axon.
• The terminal depolarises opening Ca2+ channels causing an inward flow of these ions.
• Acetyl choline (ACh) is released from the pre-synaptic terminal into the synaptic cleft.
• ACh diffuses through the cleft and binds to its post synaptic receptor.
• Sodium and Potassium channels in the postsynaptic muscle fibre open. Na+ enters, K+ leaves.
• Depolarisation causes an action potential in the second muscle fibre.
• ACh is degraded to choline and acetate by acetylcholinesterase. choline returns to the presynaptic terminal to be reused.

similarities

• use glucose and fatty acid as the main source of ATP
• striated muscle fibers.
• cylindrical muscle fibers

differences

• Cardiac muscle has 10x as many mitochondria
• Cardiac muscle stores less calcium, the change in concentration is slower therefore activation time is longer.
• No tetanus in cardiac muscle.
• no refractory period in skeletal muscle, cardiac muscle has ~200ms

Smooth muscles doesnt have sacromeres.

• Ca2+ binds to calmodulin which activates a kinase on the myosin molecule.
• the activated myosin breaks down ATP into ADP +P enabling an interaction with Actin.
• Actin polymers have tropomysin inside so their active sites are never hidden
• relaxtation takes place when the Ca2+ level falls.

Contractions are slower and less powerful than skeletal muscles.
Have a greater flexibility in length than cardiac and skeletal muscles.