some common Properties of muscle contractions (twitches)...   
   Summation - a 2nd contraction before 1st subsides  tetany*  (cause: time differential of nerve/muscle)
   Fused tetany - contraction of muscle remains constant without relaxation
   Fatigue - under repeat stimulation, contractions get feebler, lactate accumulates,
                                         pH changes lead to stopping of contractions
   Charley Horse - severe muscle cramps caused by pH imbalances, low Ca levels, & dehydration.
   Shivers - involuntary-summed muscle contractions, which releases waste heat, that warms body
  
 
  Major Muscle Types...  ability of muscle to contract is based upon MUSCLE PROTEINS*...
 
44 major types of muscle proteins: 1. MYOSINs,  2. ACTINs,  3. Troponins, &  4. Tropomyosins...
  
  1. Myosins are often Type Classed based upon the MYOSIN family protein fibers present:
                                                                     (also called heavy meromyosins*):     

       MYOSINS are  motor*proteins*  that move on actin filaments, whereas kinesin and dynein
             motors move on microtubules.  Upon interaction with actin filaments, myosin II uses
             energy from ATP hydrolysis to generate a mechanical force for movements.
       Myosin isoform types are conserved evolutionarily: 
              Comparing myosin isoform types from different mammals reveals remarkably little variation within a type from
              species to species, i.e.,  Rat Type I is more similar to Human Type I myosin, than it is to Rat Type II's. 
              Thus selective evolution has maintained a functional difference between Type I's & Type II's over eons of evolution. 

Molecular Basis for Muscle Contraction    &    Structural Model of Muscles       Vertebrate Skeletal Muscle cells are multinucleate cell*   -   muscle diagram

the SARCOMERE is a basic repeating structural unit of striated muscle...                and is defined by its banding appearance in microscopy: delimited by Z-lines...         I  band - "paler zone" around Z-line                 (Isotropic    -  passes light in all directions)        A  band - "dark region" in center of sarcomere (Anisotropic -  in different directions)        M  line - "denser" mid point of the sarcomere        H  zone - "paler zone" in the center of sarcomere around M line

myofibril***

SLIDING FILAMENT THEORY of Muscle Contraction (Hugh Huxley-1954)                    I   band varies in length becoming shorter & disappearing during contraction                   A  band remains constant in its size dimensions               contraction**                     H  Zone becomes denser during a muscle contraction

relaxed/contracted*  &  at the molecule level - actin/myosin*  contraction animation*

simple animation   &   animation*

The 4 Major Muscle Proteins interactions are responsible Contractions
1.   THICK FILAMENT     (A band - dark)          myosin II  -  a dimer twisted to form 2 helical fibers with globular heads,                                 each of which has ATPase activity*  &  an affinity to bind to actin
2.   THIN FILAMENT     (I band - light)          F-actin* -  globular protein which polymerizes into polymeric helical fibers...                             each globular actin unit contains a myosin binding site
3.      Tropomyosin* - fiber-like protein which wraps helically around thin filament                                   covering the myosin binding sites on actins
4.      Troponin* - globular protein complex which binds Ca+2 & initiates contraction cycle                                            is a complex of 3 proteins, Troponins  C, I, & T, which bind Ca;                                            Troponin C (18 kD) binds Ca reversibly...                                            Then TnC binds TnI (23 kD) & TnT (37 kD),                                            which change their conformations in response to TC binding Ca                                            causing tropomyosin to open the myosin binding sites on actin.

A description of a full Muscle Contraction Cycle, the                role of the Sarcoplasmic Reticulum,  and  Role of Ca
	1.  neuromuscular junction anatomy*	Some more anim. examples
	2.  myofibril-sarcoplasmic reticulum (ER)*	a.  Actin-Myosin bonding
	3.  Molecular Events - Ca Release***	b.  Cross bridge cycle
	4.  Muscle contraction anim*	c.   Cross bridge cycle 2
	5.  complete contraction cycle*	d.  Muscle Contraction System
	Old Spice Muscle Music

         https://www.youtube.com/watch?v=Ut-6pyIN7QE

SKIP All the MATERIAL  from this point below

             Anabolic Steroids & muscle physiology   &   Doping and Muscle Cell Growth    

 The Performance Enhancing Drugs of the Future...an>

   not steroids, but the introduction of artificial genes:    Figure*

       1.  genes for myosin type transcriptions factors,  that will activates genes
           genes for long dormant myosin isoforms of our ancient ancestors...
                                say an ancient  type IIb isoform
                                that's faster than any known Type II isoform of today

       2.  or IGF-I (insulin-like growth factor)
                         IGF-I is a growth factor structurally related to insulin and IGF-I is produced in
          response to GH and then induces subsequent cellular activities, particularly on bone growth. IGF-I
          has autocrine and paracrine activities, and like the insulin receptor, it has intrinsic tyrosine kinase
          activity. Owing to their structural similarities IGF-I can bind to the insulin receptor.

next

 Muscle Cell Growth includes:
        1.   satellite cell recruitment*, which proliferate & fuse with muscle cell fibers
        2.  pro-growth factors as IGF-I, which promotes satellite cell proliferations
        3.  growth inhibition factors, such as myostatin

Current research - H.L. Sweeney at U. Penn
        have used adeno-associated virals (AAV) to infuse IGF-I gene* into recipient muscle cells
 
    in normal mice:   experiments have overall size & growth rates up 15% to 30%
    in mice genetically engineered to overproduce IGF-I:   seen 20% to 30% larger muscle mass
                               overproduction also hastens muscle repair in mice with M.D.
    injection of AAV-IFG-I into one leg of lab rats with an 8 week weight training program
                =  2x increase in strength in treated leg
                =  longer period before gained strength is lost
                =  sedentary rats showed 15% increased strength

     Human trials for IFG-I injections to treat myotonic (prolonged contraction) dystrophy
                        are set to begin next year...
 next                                                                 to be followed by athletic gene doping?

              
ATP contraction cycle*

Training, Muscle Fiber Recruitment, &  Performance  &  Marathoner pics

    
  Muscle Performance, Training, & Fiber Recruitment

              Disuse of a muscle, as in space travel (weightlessness),
                               or a couch potato can shrink a muscle by 20% in 2 weeks.
  
              Weight Training can increase muscle mass to 150% of normal size.

  
    How do muscles get bigger and better?
 
        by making more muscle proteins...    nuclei of muscle control translation, 
                          thus one needs more nuclei, but muscle cell nuclei don't divide. 
            New nuclei come from independent adjacent cells (Satellite stem cells*).
  
            when muscles under rigorous exercise they "tear", and the damaged area 
                          attracts satellite cells into the tears, depositing more nuclei.  
             weight training thus leads to heterotrophy of muscles......  
                          more nuclei equals muscle enlargement due to more protein synthesis.
next 

  
Recruitment of Muscle Fibers   (Slow   <--->   Fast)     Is it Possible ?
                          has implications for spinal injury & athletics

    1.  Cross innervation: experimentally switch nerve innervations (slow to fast)
                        animal experiments have lead to some conversions
 
    2.  Spinal injury: a lack of nerve impulse & muscle atrophy leads to a sharp
                        decrease of the slow myosin isoform (type I), 
                        while the amount of the fast isofrom increases (type II)  table*

    Conclusion: neural input (electrical stimulation) is necessary for the 
                         proper genetic expression of the Slow - Type I isoform.
                         Electrical stimulation can reintroduce the slow fiber into
                         paralyzed muscles.

  next 

 
    3.  Weight Training and Different Myosin Types
               sedentary people have higher amounts of IIx
               active people have more IIa fibers
  
                   heavy weight-load repetitions.....
                        decreases Fast IIx fibers and converts them to Fast IIa fibers
                             nuclei stop expressing IIx gene and express IIa genes
                             after 1 month all IIx  -->  IIa    (muscle also become more massive)

     4.  Tapering - can we change amounts of  IIx  fibers?         
                 in experiments involving sedentary young adults:      
                        heavy resistance training (3 months) reduced IIx from 9% to 2%
                        but, a taper (rest for 3 months) & IIx returned above basline (9%)
                                to a level of 18%, i.e.,  more fastest twitch fibers.    fig

      5.  Can we recruit   slow  --->   fast ?   maybe...
                        but no good evidence to date for slow to fast recruitments.
    next 

                         &   muscle filament nomenclature  

  a protein called PPAR-delta, discovered by Ron Evans of Salk Institute
                                                 regulates other genes involved in fat metabolism.
             High activity of  PPAR-d burns more fat, results in leaner, more fit individuals.

  recent experiments (PLoS - Oct 2004)
              revealed that mice genetically modified to produce more PPAR-d
                      - had 2x more slow twitch (I) muscle compared to litter-mates. [fig]*
                      - PPAR-d mice could run 1,800m (2x normals) before reaching exhaustion.

              these changes are similar to those induced by sustained training & exercise
              long lasting vigorous exercise produces a higher ratio od slow twitch (I) muscle.

  a new drug (GW501516) activates PPAR-d directly leading to similar changes
                      - could help obese and heart disease patients who can't exercise.  
              GlaxoSmithKline is currently testing this drug in obese, diabetics
   end

    7.  Why muscles deteriorate with age

xxx     x
the end.                                                       el fin,            de ende,       il finito                                                       elnihaya,       telos,            finis,                                                       au revoir       farvel           a hui hou.

      atp cycle  https://www.youtube.com/watch?v=gJ309LfHQ3M