Sequence of Muscular Contraction and Relaxation

Muscle Contraction:  Simple Mechanism

1. AcH is released at the neuromuscular junction. 

2. End plate potential occurs and migrates down the sarcolemma, through the T-tubules.

3. When it arrives at the tip of the transverse tubular system, it will cause an inactive enzyme to become an active enzyme. 

As a result of that enzyme becoming active, a chemical product will be hydrolyzed (split).  It will split into two products. 

One of those products will become a chemical SECOND MESSENGER.  

That chemical second messenger will traverse the distance between the t-tubule and the terminal cisternae, and           will bind to receptors that are located on the terminal cisternae.

If enough of the receptors are activated, it will create a voltage change in the membrane of the Sarcoplasmic reticulum. 

4.  When that voltage change occurs, calcium gates will open on the sarcoplasmic reticulum. 

5.    Since the concentration is greater in the Sarcoplasmic reticulum than in the sarcoplasm, calcium will want to move down its concentration gradient into the sarcoplasm until a threshold level of calcium is reached in the sarcoplasm.

6.  Calcium will bind to troponin. 

7.  Troponin will cause a conformational change of tropomyosin, allowing for interaction between the actin and globular heads of the myosin filament. 

8.  Binding:  The myosin globular head will bind to the actin active site. 

9.  Bending: ATP located on the myosin head is hydrolyzed (broken down) to ADP by myosin ATPase.  The energy released allows the Myosin molecule to bend, moving the actin a slightly. 

10.  Breaking:  ATP reforms on the myosin head, allowing the myosin head to detach from actin.  

11.  Bouncing:  The myosin head "bounces" to then next binding site, and the process of binding, brending, breaking and bouncing continues. 

1. Action potential at the Neuromuscular junction.

2. Depolarization moves to the transverse tubules.

3. Depolarization  moves to the terminal cisternae of the SR across a significant distance of cytoplasm by activating a second messenger:
              -    Depolarization of the transverse tubule activates a membrane bound phosphodiesterase, which hydrolyzes Phosphatidylinositol to inositol triphosphate and diacylglyercol (DAG).
              -   Inositol Triphosphate diffuses to the sarcoplasmic reticulum and binds to receptors that control calcium.

4. Voltage change is sensed by dihydropyrodine receptors, which activate the ryanodine binding channels in the SR, which open and allows calcium to diffuse out rapidly.

5. Calcium channels of Sarcoplasmic Reticulum open, allowing calcium to enter the cytoplasm.  As calcium leaves the sarcoplasmic reticulum, calsequestrin gives up its bound calcium making additional calcium available.

6. The cytoplasmic calcium level increases rapidly from less than .1um to more than 10 um – a concentration sufficient to saturate binding sites on troponin.

7. Tropomyosin shifts, exposing the myosin binding sites on the G-action subunits so that the myosin-ADP and actin interact with each other

8. Binding:  The myosin globular head will bind to the actin active site.

9. Bending:  ATP located on the myosin head is hydrolyzed (broken down) to ADP by myosin ATPase.  The energy released allows the Myosin molecule to bend, moving the actin a slightly. 

10. Breaking: ATP reforms on the myosin head, allowing the myosin head to detach from actin.  

11. Bouncing:  The myosin head "bounces" to then next binding site, and the process of binding, brending, breaking and bouncing continues.