• Big picture questions for muscle:
• How does the structure of muscle differ between a sprinter, weight-lifter and a marathoner?
• Why can't an individual excel at speed, strength and distance?
• How does the body coordinate movements?
• What exactly happens when a muscle becomes trained?
• How does muscle contract?
• understand basic protein structure
• understand the interactions between the contractile proteins actin and myosin.
• How is muscle contraction regulated?
• how do nerves interact with muscles?
• how is protein activity altered?
• the role of calcium
• function of the sarcoplasmic reticulum.

• The contractile filaments (review from 1/22)
  • Arrangement of actin and myosin into thin (actin) and thick (myosin) filaments.
  • The sliding filament theory says that the filaments do not change in length themselves, but instead that they slide past each other.
  • The "ratchet" mechanism for actin / myosin sliding.  This is an example of a structural/locomotory role for proteins.
  • The role of adenosine triphosphate (ATP) in the sliding process.  This is an example of an enzymatic role of proteins.  Here myosin is acting as an enzyme by catalyzing the reaction of ATP to ADP (adenosine diphosphate) and P (phosphate), and capturing the energy that was present in the chemical bond that is broken in the process.
  • ATP produces two separate conformational changes in the myosin molecule
    • by binding to myosin, it produces a conformational changes that allows myosin to detach from actin.
    • when ATP is broken down to ADP and P, it produces a conformational change that stores mechanical energy in the myosin head group
• The length-force relationship
  • can we predict what this should be based on the sliding filament mechanism and the actin-myosin ratchet?
  • complete diagram.

• Observations - diagram
  • in a test tube, isolated actin and myosin will contract if ATP and calcium are present.
  • muscles contract in response to electrical signals from nerves that make contact with them (innervate them).
  • intracellular calcium rises during muscle contraction in intact muscle.
• The process - diagram
  • Electrical signal (action potential) moves down motor nerve
  • Electrical signal reaches interface of the nerve and muscle - the neuromuscular junction (NMJ).
  • The electrical signals triggers release of a chemical (acetylcholine) into the space between the nerve and muscle (the synaptic cleft)
  • Acetylcholine triggers an action potential in the muscle cell by binding to acetylcholine receptor.
  • The muscle cell action potential leads to release of calcium into the cytoplasm from the sarcoplasmic reticulum.
    • Normally, cytoplasmic calcium level is maintained at a low level by the activity of a calcium pump in the sacrcoplasmic reticulum membrane.
    • The calcium pump uses the energy gained by splitting ATP to ADP and P to pump calcium molecules into the sarcoplasmic reticulum.  Thus, calcium levels in the sarcoplasmic reticulum are high and there is a gradient between the cytoplasm and the sarcoplasmic reticulum.
    • When an muscle action potential enters the proper region of the muscle cell, it triggers the opening of calcium channels in the membrane of the sarcoplasmic reticulum.  Calcium will flow out of the sarcoplasmic reticulum into the cytoplasm.  Contraction will be triggered.
    • Finally, calcium will be pumped back into the sarcoplasmic reticulum by the calcium pump, this will allow relaxation to occur by removing calcium from the cytoplasm, it will also reset the calcium gradient so that the next contraction can be triggered.
    • Energy usage during muscle contraction is due both the ATP use by myosin to energize myosin heads and also due to use of ATP by calcium pumps to restore low levels of intracellular calcium and enable relaxation.
• Actin and myosin can interact in the presence of calcium. 
• In the absence of calcium, interaction between myosin and actin is prevented by the presence of a protein called tropomyosin, which covers the myosin binding sites on actin.
• When calcium levels rise, calcium binds to troponin (another protein).  The binding of calcium changes the shape (conformation) of troponin.  In turn, troponin interacts with tropomyosin and changes its conformation such that it no longer prevents actin-myosin interaction.
• Contraction can occur until calcium falls away from troponin.