a correlation of Form vs. Function 

The response of a Reflex Arc & Correlation of Structure & Function...
                     Campbell 12e reads: C50: (pg 1125-1132)  &  Campbell 11e reads: C50 (pg 1123-1129).

         Model:   vertebrate skeletal neuromuscular junction
                                -  striated skeletal muscle cell*    pic      myoblasts (muscle cells)
                                -  innervated muscle fiber*       
   pic       neuromuscular junction


     Muscles cannot stretch (pull), they may  only CONTRACT  (get shorter via a pull)
              contractions provide forces that move bones acting as levers (fulcrum point).

              A muscle CONTRACTION is also called a muscle
4 parts of a Slow Twitch Muscle Contraction        CONTRACTION  CYCLE* 
 1) latent period - 5 msec  time between application of AP & initiation of contraction
 2) contraction - 40 msec  muscle shortens & does its work
 3) relaxation - 50 msec  muscle elongates & returns to original position
 4) refractory period - 2 msec  time of recovery between stimulations of muscle 







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. 









Besides classifying muscle based on the type myosins present  (different isoforms)
    muscle are often classified on the speed of contractions into
2 Muscle Fiber Types:
    which are determined both genetically & functionally. 

         TYPE I (Slow Twitch muscles)      &      Type IIa/IIx (Fast Twitch muscles)   

       Classification is based upon how fast they can produce a contractile twitch.

            all muscles are composed of varying % composition of these two types
slower contraction times (100-110 mSec) faster contraction times (50 mSec)
tonic muscles (darker:  red) - leg muscles tetanic muscles (paler: white) Pectoral (chest) muscles
contain myoglobin (red) no myoglobin (white)
continuous use muscles - prolonged performance
endurance performances ( marathoners)
one time use muscles - brief performances
         ... for power & speed (
*  predominantly AEROBIC enzymes & metabolism
          ... cell respiration pathways

*  predominantly ANAEROBIC (glycolysis)
         ... easily converts glycogen to lactate  w/o O
marathoner:    80% type I   &   20% type II sprinter:    20% type I   &   80% type II 
                    Distribution of Slow & Fast Twitch muscle in Humans              
tropinin has lower affinity for Ca troponin - higher affinity for Ca















Relative Distributions of Slow Twitch & Fact Twitch
Skeletal muscle Subtypes -
Type I & Type II)
  Type I (slow) Type II (fast) Type IIa Type IIx
Average person 50% 50% 40%  10%
sprinter 20% 80% 45% 35%
marathoner 80% 20% 20% 0%
couch potato 40% 60% 30% 30%
spinal injury 4% 96% 48% 48%
Due to the conserved evolutionarily stabilty of myosin types they can not be converted,
thus a spinal cord injury cannot be repaired by converting Type II myosins to Type I's.














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 
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                                                







                                               A short Summary

                      Top 18 fundamental Biology Concepts every
                             college biology student should know*     

                               The Future of Biology, Especially Human Biology

                                              the end

         copyright c2023       
       Charles Mallery
,    Biology 150, Department of Biology,  U. of Miami,  Coral Gables, FL 33124



























SKIP All the MATERIAL  from this point below

             Anabolic Steroids & muscle physiology   &   Doping and Muscle Cell Growth    


 The Performance Enhancing Drugs of the>

   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.






 Muscle Cell Growth includes:
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

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
    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?




    Myostatin... is a muscle inhibitory growth factor [blocks muscle growth],
                                  myostatin is also called GDF-8 (growth differentiation factor)
                        it promotes atrophy and slow muscle cell growth,
may function antagonistically with IGF-I, which promotes muscle growth.
       described by A.C.McPerrron & Se-jin Lee at Johns Hopkins in 1997
defective myostatin genes = considerably larger muscle mass
Belgian Blue cattle*   and   the Breed & its cause
                                              a human case study*  -->


             may be useful in muscle debilitating diseases, which include:
                                   muscular dystrophy -
                                   sarcopenia - age realted muscle loss
                                   cachexia - aggressive muscle loss in cancer & HIV patients
                                   myoclonus - abnormal muscle contractions
            Wyeth pharmaceuticals is at work on myostatin inhibitors
                              1st drugs to date are antibodies to myostatin and
                               some clinical trials are set to begin in M.D. patients


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.





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

    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.




    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.


                         &   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

    7.  Why muscles deteriorate with age


xxx     x     
thats all

                                       the end.

                                                      el fin,            de ende,       il finito

                                                      elnihaya,       telos,            finis,

                                                      au revoir       farvel           a hui hou.







best in long slow sustained contractions best in rapid (short) contractions 
not easily fatigued easily fatigued
more capillary beds, greater VO2 max  less capillary beds
smaller in size larger in size
lower glycogen content higher glycogen content
poor anaerobic glycolysis poor but some aerobic capacity
higher fat content lower fat content 
more mitochondria - Beta Oxidation high fewer mitochondria- Beta Oxidation low
poorly formed sarcoplasmic reticulum well formed sacroplasmic reticulum
slower release of Ca = slower contractions quick release of Ca = rapid contractions 
tropinin has lower affinity for Ca troponin - higher affinity for Ca






      atp cycle