1. Generally attached to skeleton.

2. Voluntary, nerves (motor neurons) usually signal for contraction.

3. Fast contracting but generally can not sustain contraction.

4. Striated, long and skinny, multinucleated. Single cell goes the length of the muscle.

1. Heart muscle

2. Involuntary (generally) to a degree self contracting.

3. Fast, can withstand infinite repeated contractions.

4. Some degree of striation, single nucleus, somewhat long, often branched.

1. Found around "tubes" of the body (digestive, circulatory)

2. Involuntary.

3. Slow, sustained contractions.

4. No striations, single nucleus, oblong in shape.

1. Not part of the muscle, but an important part of its function is the motor neuron (nerve cell) that has one end attached to each muscle cell (the other end of the motor neuron usually is in the brain-remember these are voluntary muscles).

2. The neuron contains packets of a neurotransmitter called acetylcholine. This is a small molecule made out of acetic acid and choline.

3. There is a small gap between the neuron and the muscle cell called the neuromuscular junction.

4. The muscle side of the neuromuscular junction (postsynaptic terminal) has embedded in the sarcolemma (plasma membrane) are receptors designed to accept acetylcholine. These receptor molecules are made out of protein.

5. The sarcolemma forms invaginations deep into the cell (the invaginations are referred to as the T-system.) The T-system comes in close contact with the sarcoplasmic reticulum (endoplasmic reticulum).

6. The sarcoplasmic reticulum has a powerful Ca++ pump that keeps the concentration of Ca++ inside the sarcoplasmic reticulum at a level about 2000 times higher than in the sarcoplasm (cytoplasm). The sarcoplasm also has electrosensitive Ca++ gates and presumably work much the same as Na+ and K+ gates work.

7. Back to the muscle cell as a whole: Each muscle is a family of cells (each cell generally the length of the muscle) surrounded by connective tissue and attached to bones by connective tissue (bundles of collagen known as tendons).

8. The muscle itself looks patterned, and the muscle cell (=muscle fiber) itself exhibits striations.

9. Each muscle cell fiber (10-100 µm x 30 cm) is made up of many fibrils (or myofibrils) surrounded by the other cellular constituents, .

10. Each fibril can be divided from Z line into units of sarcomeres (about 2 µm long). The Z-line itself is made of protein.

11. Actin made up of two helical strands attached to the Z line. (thin filaments)

12. Myosin made up of many individual myosin protein molecules layered parallel upon each other. Each myosin molecule has a lollipop looking structure that demonstrates ATPase activity and also has the ability to attach actin. A band - length of myosin (thick filament).

13. Myosin and actin are the two major protein components of muscle.

1. Resting membrane potential (~-70mv) exists for the neuron. The acetylcholine is sitting in small vesicles floating in the cytoplasm of the nerve cell ready to be released upon command.

2. Resting membrane potential (~-70mv) exists for the muscle cell.

3. Ca++ is in high concentration in the sarcoplasmic reticulum.

4. ATP is bound to the myosin, but the myosin can not bind to the actin because the tropomyosin is in the way. The muscle is flaccid or elastic in this condition.

a. In reality muscles of a living person are never completely in this condition. Muscles are always in a state of even mild contraction called tone.Muscles are probably most relaxed when we are asleep.

1. Brain sends a signal down a motor neuron for contraction (in the form of an action potential)

2. When the signal reaches the end of the nerve, it causes an uptake of calcium.

3. The calcium uptake stimulates the release of acetylcholine into the neuromuscular junction.(Sir Bernard Katz) The acetylcholine is released in packets by exocytosis.

4. Acetylcholinesterase immediately starts to break down the acetylcholine into acetic acid and choline. However, some diffuses across the neuromuscular junction to attach to receptor proteins located on the muscle cell membrane.

5. The binding of the acetylcholine to these membrane proteins causes the membrane to become leaky to Na + ions (similar to, but not the same as Na+ gates.)

a. Curare (dart poison) binds to these receptors and prevents acetylcholine from binding thus preventing any muscle contraction.

6. As the Na+ leaks it causes a depolarization which stimulates adjacent Na + and K+ gates to open, thus starting an action potential in the muscle cell.

7. The action potential will propagate in both directions from this initial point. As the action potential propagates along the muscle cell membrane (sarcolemma) it will also weave in and out of the T-tubule system of the sarcolemma.

8. The T-Tubule system comes in close proximity to the endoplasmic reticulum (sarcoplasmic reticulum) inside the cell.

9. Some how this stimulates the opening of Ca++ gates, allowing a large flow of calcium out of the sarcoplasmic reticulum into the cytoplasm (sarcoplasm).

10. The calcium gets into the sarcomeres and binds to receptor sites on the troponin molecules (which are resting on the tropomyosin and actin filaments). The binding of the calcium causes a shape change in the troponin protein such that it leads to a shape change in the tropomysosin molecule. The tropomyosin is changed in shape such that it uncovers the actin and exposes the myosin binding site that resides on the actin. The myosin can now bind to the actin. (Normally troponin-tropomyosin blocks the binding of myosin to actin).

11. The myosin, with an already bound ATP molecule, binds to the actin.

12. As the ATP reacts to form ADP, the released energy is used to bend the myosin head such that the actin filament slides along relative to the myosin filament. During contraction the filaments of actin and myosin not change length but the distance between Z bands does. Thus developed the sliding filament theory versus contracting proteins.

13. The ADP is dropped by the myosin, myosin binds another ATP and only then does it release from the actin. The process is repeated. Several repetitions cause a significant movement. At full contraction the myosin is still trying to pull on the actin and ATP is still being used.

Exceptions:

a. Rigor mortis is where ATP is not available and the myosin can not release from the actin. Certain types of cramps are caused by the same phenomenon.

b. The catch muscle of molluscs remains full contracted without use of energy by somehow maintaining the myosin-actin bonds.

14. This continues until the action potentials stop

1. Action potentials stop coming from the brain down the motor neuron, thus acetylcholine is no longer released.

2. The always present acetylcholinesterase in the neuromuscular junction chews up the last of the acetylcholine. (The acetic acid wanders off and gets used by cells in the Kreb's cycle. The choline gets reabsorbed so it can combine with a newly made acetic acid molecule in the motor neuron.)

3. Without any acetylcholine, the action potentials in the muscle stop.

4. Without any action potentials in the muscle (and the T-system), then the Ca++ gates of the sarcoplasmic reticulum can close.

5. The Ca++ active transport pumps (which were working constantly all along) are no longer overwhelmed by the leak and thus they successfully pump calcium from the sarcoplasm back into the sarcoplasmic reticulum.

6. Without bound Ca ++ the troponin-tropomyosin regain their resting shape. The very next time the myosin releases from the actin, the troponin-tropomyosin will sneak back in between and prevent any further interaction between the actin and myosin.

7. Without the the actin myosin bonding, the sarcomeres and muscle can no longer contract, thus the muscle elastically moves back to its resting position (or more commonly , is passively pulled to a new position by a more dominant antagonistic muscle)

ATP + H 2O -------> ADP + H 3PO4 + energy

1. Myosin ATPase.

2. Na+-K+ ATPase for developing a membrane potential (sarcolemma and nerve cell)

3. ATPase for sarcolemma Ca++ pump.

After the reserves of ATP are used, the first indirect source of energy generally used is Creatine phosphate (CP):

2. Next, glucose is used as an energy source:

a. ANAEROBIC glucose breakdown to make ATP.

After the exercise, the amount that has to be oxidized is the amount necessary to bring the ATP, CP, lactate and the rest of the muscle back to homeostasis. This exactly corresponds to the amount of exercise that was done and the amount of oxygen necessary to reachieve this homeostasis is called the oxygen debt.

b. AEROBIC glucose breakdown to make ATP.

c. Glucose source. Often the amount of glucose stored as such is not sufficient for repeated muscle contractions. More glucose can be derived from stores of glycogen in the muscle itself and in the blood. The liver also plays a very important role in converting glycogen to glucose. The conversion of glycogen to glucose is relatively rapid compared to other methods of glucose formation (e.g the development of glucose from fats would be very slow).

3. As a last ditch energy source, the ADP can be used in an unusual fashion to make ATP using the enzyme myokinase:

2 ADP ----> ATP + AMP

1. The red in red fibers comes from MYOGLOBIN which binds oxygen IN the muscle cell and is consistent with these types of cells undergoing more endurance. The myoglobin also facilitates oxygen diffusion from the blood to the mitochondria.

1. The speed of a muscle is directly proportional to its length. Speed is a distance covered per unit time. In comparing a long muscle to a short muscle, the time it takes for individual sarcomeres to contract in each is unchanged, however the contraction will occur over a longer distance in the longer muscle. Thus, in one second, a much larger distance can be covered.

2. The strength of a muscle is directly proportional to its cross sectional area. The more cross section there is the more actin-myosin cross bridges one has to fight against. (Increasing a muscle in length does not increase its strength no more than does increasing a string in length increase its strength).

3. Trade offs between strength and speed can be made by using the bones as levers. (page 224-225).

a. For example, the biceps control the movement of the hand; the lever system allows a much larger range of movement of the hand whereas the biceps itself only moves over a small range. This large movement occurs in the same time that it takes the biceps to contract. Thus, because of the levers the hand moves much faster (larger distance per unit time) than does insertion end of the biceps itself. However, the hand can left very little weight compared to the weight that could be lifted if attached directly to the biceps insertion itself.

b. Conversely there are some lever systems in the foot that favor strength over speed.

1. A Stimulation is anything that causes the desired response. (An artificial stimulation is usually a voltage change).

2. A twitch is the quick, single muscle contraction caused by a single, brief stimulation.

[Demonstration - using flexor digitorium muscle

frequency => 1 event/sec

duration => 0.40 ms

stimulus => 65 volts

sweep speed => 3 sec/sweep

Increase events to show the loss of twitch.

1. If all-or-none was perfect then the following will be the case: Below a threshold stimulus no response (contraction) occurs; at threshold a complete response (contraction) occurs; for all stimuli above threshold you get the exact same response that you had at threshold.

2. In reality, muscle does not show perfect all-or-none, there are some gradations:

[ Demonstration - show all-or-none and determine a threshold

value; use the light spring]

frequency => 1 event/sec

duration => 0.40 ms

stimulus => start at 40 v

sweep speed => 15 sec/sweep

Turn voltage up beyond threshold.

Turn voltage back down below threshold.

Review data.

1. LAG TIME - about 4 ms; due to all of the things that must happen before the sarcomeres actually start to contract.

2. CONTRACTION TIME - actual myosin-actin interactions.

3. RELAXATION TIME - the time to remove all of the cytoplasmic calcium, etc. The relaxation time is always slower than the contraction times.

4. All of these times heavily depend upon the particular muscle in question.

[ Demonstration - show twitch timing]

set up twitch mode

light spring

frequency => 1 event/sec

duration => 0.40 ms

stimulus => start at 40 v

sweep speed => 3 sec/sweep

[ Demonstration - show summation]

change back to regular mode

change to medium spring

frequency => 1 event/sec

duration => 0.40 ms

stimulus => 65 v

sweep speed => 3 sec/sweep

increase frequency to 50 events/sec

1. TREPPE - the gradual staircase increase in contraction due to repeated rapid stimulations.

2. TETANUS - the smooth, sustained, maximal contraction due to repeated rapid stimulations.

3. FATIGUE - loss in contraction ability; the magnitude decreases after several contractions.

1. When the muscle is almost fully extended it has very little strength because the myosin can not make a lot of contract with actin

2. When the muscle is almost fully contracted it has very little strength because the myosin can not make a lot of contract with actin because the actin is overlapping itself:

3. When the muscle is at mid extension is when myosin and actin have maximal opportunity to interact and do something:

1. Speed = distance over time. The time of each sarcomere contraction will not change. Putting many sarcomeres in series will increase speed because of the greater DISTANCE of shortening.

SPEED a LENGTH of muscle

2. Strength = the number of actin myosin interactions in a cross sectional area.

STRENGTH a CROSS SECTIONAL AREA of the muscle

(Note that length of muscle has nothing to do with strength; e.g. a chain is only as strong as its weakest link, making it longer makes it no stronger)

3. Work = force X distance

Since force is proportional to the cross sectional area and distance is proportional to length, then force times distance will be proportional to volume or (mass).

1. Consider a muscle that can do 200 Kg-cm of work, it takes 200 msec to contract and it can directly maximally lift 200 kg:

2. Levers can not change the amount of work a muscle can do (work = force times distance) but it can change the proportion that is devoted to distance verses force.

a. Consider the same muscle arranged as below (much like your biceps). The advantage is greater distance (which also translates into greater speed). The disadvantage is the amount of weight that can be lifted.