Introduction to Organismal Biology (BIOL221) - Dr. S.G. Saupe; Biology Department, College of St. Benedict/St. John's University, Collegeville, MN 56321; ssaupe@csbsju.edu; http://www.employees.csbsju.edu/ssaupe/

Muscles:  Structure & Function

I. Muscle Structure
    Muscles are comprised of bundles (fascicles) of muscle fibers (actually cells). The muscle fibers are surrounded by connective tissue.  

A. Muscle Fiber (cells)

• long (can run entire length of muscle)
• cylindrical
• multi-nucleate
• sarcolemma (=plasma membrane), sarcoplasmic reticulum (=endoplasmic reticulum), sarcoplasm (= cytoplasm)
• T-tubules – inward extensions of the sarcolemma
• contains bundles of myofibrils
• organization summary:  muscle (tissue) � fibers (cells) �  myofibrils � myofilaments

B. Myofibrils

• threads that run through the muscle fibers
• made of actin and myosin myofilaments (or just filaments)
• myosin filaments – thick; myosin (contractile protein); head and tail region; look like golf clubs
• actin filaments – thin; actin (contractile protein; globular units, called G-actin, linked together to form a chain, called F actin; two chains intertwined); associated with regulatory proteins (tropomyosin, troponin complex) attached at intervals
• actin and myosin filaments overlap to form a sarcomere
• numerous sarcomeres are joined end-to-end to form a myofibril

C. Sarcomeres

• contractile units
• thick myosin filaments in middle region
• thin actin filaments toward outside
• distinctive striated structure of sarcomere due to overlapping of the thin (actin) and thick (myosin) filaments and attachment of adjacent sarcomeres. The following regions of the sarcomere can be seen (check diagram in text): 

1. Z-line (region where adjacent sarcomeres are attached through by joining their thin filaments);
2. I band (lighter area with only thin filaments)
3. H zone (central zone with only thick filaments)
4. M line - dark area in the H zone, region where myosin tails are joined
5. A band (regions where thick and thin filaments overlap)

II. Muscle Contraction
    Muscles contract as the actin and myosin filaments slide past one another. Note that the filaments do not decrease in length. Sliding requires energy that is supplied by ATP. The myosin head of the thick filaments is the "business" end of the process and contracts moving (like a ratchet) the thin filaments toward the middle of the sarcomere. This is called the "Sliding Filament Model".  Let's see how it works:

1. ATP binds to the myosin head at a specific binding site
   
2. Myosin hydrolyzes the ATP into ADP & Pi. (note that the myosin is an ATPase). Some of the energy is used to change the position of the myosin from a "bent" low-energy state, to an "open" high-energy state; releases myosin from the actin filament
   
3. Energized myosin binds to an available site on the actin filament
   
4. ADP & Pi are released from the myosin head and this causes the head to "spring back" to its original bent configuration moving the actin filament toward the sarcomere center.

III.  Muscle Relaxation
    The muscle fibers return to their original position - pulled back by the 'elasticity' of the muscle.  As the muscle contracts it acts a little like stretching a rubber band ultimately pulling the muscle back. 

IV. Regulation/Control
    Skeletal muscles only contract when stimulated by a motor neuron. Muscle fibers don't normally contract because the myosin binding sites are normally blocked by regulatory proteins (troponin/tropomyosin complex). For contraction to occur, the tropomyosin/troponin complex must be moved out of the way. How does this work?

1. Motor neurons extend to each skeletal muscle
        One motor neuron may activate from a dozen to many muscle fibers
        The motor neuron doesn't attach directly to the fiber, but ends in a synapse
   
2. The electrical signal from the neuron reaches the end of the neuron (axon) stimulating the release of a chemical neurotransmitter - acetylcholine
   
3. Acetylcholine diffuses across the synapse and activates chemical-gated channels in the post-synaptic membrane in the sarcolemma of the muscle fiber
   
4. Ions (sodium) enters the muscle fibers which causes a depolarization of the membrane (switches polarity).
   
5. The wave of depolarization sweeps down the muscle fiber (= action potential)
   
6. The action potential spreads through the T (transverse) tubules (I'll bet you were wondering what those were for!) and into the sarcoplasmic reticulum.
   
7. In response, the SR releases calcium ions into the myofilaments
   
8. Calcium binds to the troponin complex which alters the shape of the tropomyosin/troponin complex causing them to pull away from the binding sites on the actin thin filaments
   
9. The exposed active sites can now bind with the myosin for contraction
   
10. Calcium pumps, via active transport, continually move calcium from the sarcoplasm back into the SR.

V. Energy Source for Contraction

1. ATP – this is the readily available energy source. It's like the money in your pocket. Like your cash, the ATP goes fast and there is usually only enough for a few contractions. ATP is generated by the mitochondria – hence lots of big ones in muscle fibers. This is also why lots of oxygen is required for muscles.  No ATP = rigor mortis.
   
2. Creatine phosphate – a backup energy source that provides phosphate for ATP. Like ATP it is also quickly used up. Perhaps analogous to a traveler's check that you can easily convert to cash.
   
3. Glycogen – a polymer of glucose; a storage form of energy. This is like having money in the bank.  You can access these funds with a credit card or check.  It is used for repetitive contractions and can be "used up".

VI. Graded Contraction
    Here's a paradox – we know that we can voluntarily alter the extent and strength of a contraction (a graded response), BUT at the cellular level the response is all-or-nothing. How are graded contractions generated? It is controlled by the nervous system that:

1. can vary the number of action potentials in the motor neurons. A single action potential causes a single "muscle twitch". If a second action potential arrives before the first one ends, then the responses add up further stimulating the muscle. If enough action potentials are received the muscle shows one smooth sustained contraction (tetanus – not the same as disease).
   
2. can vary the number of muscle fibers that are activated

VII.  Cell Type - a refresher
    Muscle cells: (a) are elongated; (b) excitable; and (c) can contract. Recall that there are three major types of muscle cells/tissue:

1. Skeletal
       Responsible for voluntary movements. These cells are long and cylindrical, and when bundled together form fibers, which in turn are sheathed into a muscle. Skeletal muscle is striated and multi-nucleated.  Activated by motor neurons.
   
2. Smooth
       Involved in involuntary movements. These cells are tapered (spindle shaped) and are important in blood vessels, stomach, bladder, and internal organs. Smooth muscle is not striated because actin and myosin are not regularly arranged as in skeletal muscle.  There is only a single nucleus. The cells occur in sheets; electrical synapses (gap junctions). 
   
3. Cardiac
       Involuntary contractions. Found in the wall of the heart (where else?).  Striated.  The cells are branched (withstand pressure and resist tearing) and are fused (intercalated disks) for intimate contact.  Electrical synapses.  Single nucleus.

VII. Cool Stuff

• Slow twitch fibers – longer sustained responses; endurance athletes; most of the ATP generated by aerobic respiration - evidence:  have lots of mitochondria; enriched with myoglobin (pigment like hemoglobin), makes the slow-twitch fibers reddish in color.  The myoglobin provides additional oxygen for aerobic respiration; Myoglobin type I.
  
• Fast twitch fibers -  short rapid bursts of activity; sprinters; fewer mitochondria, ATP can be generated by anaerobic metabolism (e.g., fermentation); little myoglobin, whitish in color.
  
• Muscles can only contract - thus, to move back and forth requires two muscles acting oppositely of one another. For example, when the biceps contracts the arm bends; when the triceps contracts, the arm extends.