Lec 5 Physiology Dr. Hanan Luay
The muscle
Objectives
1-Describe the characteristics of skeletal muscles?
2- What are the structural changes observed during contraction?
3- What is T system and its role in the contraction of skeletal muscle?
The muscles are excitable cells; they are machines to convert the chemical energy to mechanical energy.
The muscle can be excited electrically, mechanically, chemically → action potential (A.p.).
It differs from the nervous system by the fact that it has a contractile mechanism which is activated by action potential.
Types of muscle:
1-Skeletal muscles: These are voluntary muscles attach to bones except the tongue, superior portion of the esophagus, anal sphincter are also composed of skeletal muscles, but they do not cause movements of the skeleton.
Skeletal muscles Smoothmuscles Cardiac muscles
2-Smoothmuscles: Involuntary muscle. It is Muscle of the viscera (e.g., in walls of blood vessels, intestine, & other 'hollow' structures and organs in the body).
3-Cardiac muscles: Muscle of the heart. Involuntary.
40% of the body is skeletal muscles and 10% are smooth and cardiac muscles.
Characteristics of muscle:
- excitability - responds to stimuli (e.g., nervous impulses)
- contractility - able to shorten in length
- extensibility - stretches when pulled
- elasticity - tends to return to original shape & length after contraction or extension.
Functions of muscle:
- motion
- maintenance of posture
- heat production
The skeletal muscle:
It is that type of the muscles that is attached to bones & moves skeleton, also called striated muscle (because of its appearance under the microscope), it lacks anatomical and functional connection between individual muscle fibers, and it is voluntary muscle (under voluntary control).
Morphology:
It is composed of numerous fibers (building units of the muscular system), which is made up of smaller subunits.
Each muscle fiber extends along the length of the muscle, and each is innervated by one nerve fiber near the middle of the fiber.
The muscle fibers are arranged in parallel between the two tendon ends, so that the force of contraction is additive also this allows each fiber to be controlled individually so we can contract fewer or more fibers and the strength of contraction will be graded.
The muscle fiber is a cylindrical single cell containing:
-multiple nuclei.
-Cell membrane (sarcolemma) fuses with the tendons at the muscle ends.
-Sarcoplasm (intracellular fluid fills the spaces between the myofibrils {K+, Phosphate, protein enzymes and mitochondria, sarcoplasmic reticulum which controls the contraction(rapid contracting muscles means extensive reticula)}
-Other organ cells
-Small muscle fibrils, which consist of filaments that are made up of contractile proteins (actin and myosin).
Actin and myosin are large polymerized protein molecules, responsible for actual muscle contraction.
The striations:
The myosin and actin filaments interdigitate and cause the myofibrils to have alternate light and dark bands.
The light bands are only Actin filaments called I bands, they are isotropic to polarized lights.
The dark bands contain Myosin (twice molecular weight of Actin) called A bands; they are anisotropic to polarized lights, overlapping with Actin filaments. (It does not change in contraction), each thick filament is surrounded by 6 thin filaments in a regular hexagonal pattern.
So the striations are due to difference in the refractive index of the parts of the muscle fibers.
The I band is divided in the middle by darker Z line (the actin filaments are attached to the Z disc from which the filaments extend in both directions to interdigitate with the myosin).
The A band is divided by the lighter H band, in the middle of it there is a line called M line.
On the ends of the myosin filaments are small projections called the cross bridges, which interact with the actin filaments to cause contraction.
The portion of the myofibrils (or the whole muscle fiber) that is between 2 successive Z discs is called Sarcomere.
On contraction, the length of it is about 2 micrometer (the actin completely overlap the myosin, the tips of actin are just beginning to overlap one another.
The sarcomere is the smallest functional unit of the muscle; it is the area between 2 Z lines. It increases in relaxation and decreases in contraction.
Molecular charectristics of the contractile filaments:
Myosin filaments
It is composed of 6 polypeptide chains, a/ 2 heavy (wrap spirally around each other to form double helix called tail, one end of these chains is folded bilaterally into a globular polypeptide structure called head (2 heads) with 2N terminals, they contain actin binding sites and a catalytic site that hydrolyse ATP and, b/ 4 light chains (are parts of the head (help control the function of the head during contraction).
The tails are bundled together to form the body of the filaments, while many heads hang outwards from the body.
Part of the body with the head extends to form arms (called the cross bridges). There are no cross bridges in the middle of myosin filaments because the hinged arms extends away from the center.
The cross bridges are flexible at 2 points one where the arm leaves the body, the other where the head attaches to the arm, these called hinges.
The thin filament is made of actin ,torponin and tropomyosin.
Actin molecules:
Actin filament is made up of 2 chains of globular unit that form a long double helix and contain binding sites for myosin. It is composed of double stranded F actin protein molecule made in a helix, each strand is composed of polymerized G actin molecule ,attached to each one molecule of ADP , these are the active sites with which the cross bridges of myosin interact.
Tropomyosin molecule
They are located in the groove between the two chains forming long filaments overlying the binding sits of myosin. So in the resting state they lie on the top of the active sites of the actin strands so no attraction between actin and myosin.
Troponin
It is a protein attached intermittently at regular intervals along the sides of tropomyosin molecules. It is a complex of 3 loosely bound protein subunits:
Troponin I has a strong affinity for actin inhibits the interaction between myosin to actin.
Troponin T binds troponin to tropomyosin.
Tropomyosin C contains binding sites for calcium ions that initiate contraction.
The troponin- tropomyosin complex is called the relaxating protein, because it prevents the binding of actin to the heads of myosin and leads to muscle relaxation.
The sarcotubular system:
Because the skeletal muscle fiber is so large, the action potential cannot flow deep within the muscle fiber to cause maximum muscle contraction, current must penetrate deeply into the muscle fiber, and this is by:
The T system (transverse tubules): it is a system of transverse tubules in the form of letter T which is continuous with the membrane of the muscle fiber, it starts from one side of the cell membrane to the opposite side, so it is continuous with the extracellular space, and they contain extracellular fluid inside ; they are present along the whole length of the muscle fiber and is responsible for spreading of action potential from the cell membrane to the interior of the muscle fiber, the electrical currents around them create the muscle contraction.
The sarcoplasmic reticulum : it forms an irregular system of tubules surrounding the myofibrils it has an enlarging ends or chambers called terminal cisterns in close contact with the T system at the junction between A and I bands.
The arrangement of the T system with the ciatern of the endoplasmic reticulum at either side called Traid.
The sarcoplasmic reticulum contains excess amounts of calcium ions (in the cistern) in high concentration which are released when the action potential occurs in the adjacent tubules. After the contraction has been occurred ,active calcium pump located in the walls of sarcoplasmic reticulum pumps calcium back to the sarcoplasmic tubules (inside the reticulum there is a protein called calsequestrin which can concentrate and binds up to 40 times more calcium ions). In addition to that the terminal cisterns help in muscle metabolism.
Lec 6 Physiology Dr Hanan Luay
Objectives
1-What does simple muscle twitch represent?
2-How can the contraction of skeletal muscle be explained?
3-What are the types of contraction of skeletal muscles?
Electrical characteristics of skeletal muscles:
1- The resting membrane potential is – 80 to – 90 mill volt in skeletal muscle fiber (same as in large mylinated nerve fiber).
2- The electrical changes of the ion fluxes are similar to those of the nerve fiber during action potential.
3- Duration of the action potential is 1 to 5 milliseconds (5 times longer than that in mylinated nerve fiber).
4- The conduction velocity is 3 to 5 m/ second (less than that in large mylinated nerve fiber).
5-Due to the slight difference in the threshold between muscle fibers of the same muscle and the difference in the distance between the stimulation site and different muscle fibers, the action potential recorded from the whole muscle after direct stimulation is proportional to the intensity of the stimulus between threshold and maximum intensity (do not obey all or none law for the whole muscle but not for a single muscle fiber which obey this law).
6- Each single contraction is followed by a single relaxation in response to a single action potential (simple muscle twitch).
Simple muscle twitch:
Is a single contraction followed by single relaxation in response to action potential .It is measured usually by a device called Myogram.
The shape is consisted of contraction phase which is preceded by latent period (lag phase), then there is the relaxation phase.
The shape of the single muscle twitch is:
Excitation contraction coupling
1- Sliding filament theory:
The process by which depolarization of the muscle fiber initiates contraction is called excitation- contraction coupling. It occurs in the following steps:
1 – The discharge of motor neuron.
2- An action potential travels along the motor nerve to its ending in the muscle fiber.
3- Secretion of small amounts of neurotransmitter substance Acetylcholine (Ach) at the motor end plate.
4-Ach binds to nicotinic receptors on muscle fiber membrane to open Ach gated channels.
5- Increase in Na ions conductance (Na ions diffuse to the interior of the muscle fiber membrane) and this will initiate a local end plate potential, and when firing level is reached, action potential is generated and spread along the whole muscle fiber.
6- The inwards spread of the action potential by the T system of tubules.
7- Release of calcium ions from the terminal cisterns of the sarcoplasmic reticulum.
8-Calcium will bind to Troponin C molecule this will lead to conformational changes:
The binding of Troponin I to actin will be weakened.
This allows Tropomyosin to move laterally outside the groove and uncover the binding sites for the myosin heads.
So Ca ions will act as an inhibitory factor on troponin –tropomyosin attachment to actin.
ATP molecule will split to produce energy (degenerated to ADP) for the contraction. 7 Myosin heads are uncovered for each molecule of Troponin that binds to single Ca ion.
The formation of cross bridges between actin and myosin heads → sliding of thin on thick filaments producing shortening (the sarcomere will be shortened).
The width of A band is constant, whereas Z lines move closer when the muscle contracted and apart when the muscle stretched.
So during muscle contraction 1- the Z lines move closer to each other,2- the I band becomes shorter and 3- the A band stays at the same length.
2- The walk- along or Rachet theory of contraction:
This theory suggests that the sliding during muscle contraction is produced by attaching, breaking and reforming of the cross linkages between actin and myosin heads, the intensity of the interaction depends on the number of cross linkages .
After uncovering of the active sites of the actin ,myosin head link to actin at 90 degrees angle(then decreasing the angle because energy liberated) producing movement by swiveling(pulling) and then disconnect and reconnect at the next linking site repeating the process in a serial fashion(i.e. after the head attaches to the active site, it produces profound changes in the intramolecular forces between the head and the arm , the new alignment of forces causes the head to tilt towards the arm to drag the actin filament along with it, automatically after tilting the head breaks away from the active site, then the head returns to its extended direction , then it combines with a new active site farther down along the actin filament , the head tilts again to form another power stroke and then the actin filament moves another step
Each single cycle of attaching, swiveling and detaching shortens the muscle fiber by 1%of its length.
Each thick filament has about 500 myosin heads, and each of these cycle 5 times /second during rapid contraction. The pulling of the heads of myosin to actin or the tilt of the myosin head is called the power stroke.
Power stroke of myosin in skeletal muscle. The myosin head detaches from actin (top), moves several nm along the actin strand, and reattaches (middle). The head then flexes on the neck of the myosin molecule (bottom), moving the myosin along the actin strand.
Steps in relaxation:
1- After a fraction of a second, the calcium ions are pumped actively back into the sarcoplasmic reticulum by a Calcium membrane pump (active transport, needs ATP i.e. both contraction and relaxation need energy)they are going to diffuse into the terminal cisterns to be released by the next action potential.
2- The release of calcium ions from Troponin C,
3- Then cessation of binding between actin and myosin (i.e. tropomyosin returns to its site) this removal of calcium ions causes the muscle contraction to stop.
If Ca ions stay in high concentration outside the SR, or if the Ca ions transport to the SR is inhibited, there will be persistent contraction and no relaxation even though there are no more action potentials and this will result in what is called contracture (sustained contraction).
Characteristics of whole muscle contraction:
Types of contraction:
1- Isomertic contraction: is when the muscle does not shorten during contraction i.e. no change in muscle length, but the tension will increase. The muscle contracts against a force transducer without decreasing the muscle length. e.g. trying to lift a heavy object. The work done here is zero, because no movement.
The isometric contraction records the changes in force of the muscle contraction itself, it is used to compare the functional characteristics of different muscle types.
2- Isotonic contraction:
It is the contraction that causes shortening of the muscle length and the muscle has the same tension. e.g. lifting an object by contracting the biceps muscle.
Here there is work done because there is movement.
The muscle shortens against a fixed load, and its characteristics depends on the load against which the muscle contracts and on the inertia of the load.
Lec 7 Physiology Dr. Hanan Luay
Objectives
1-Does contraction summate and why?
2- How can length be related to force of contraction?
3- What are the energy sources for the muscle and for what it is used?
4- Describe the motor unit and how its type affects the function of the muscle?
The summation of contraction:
The strength of a muscle’s contraction is influenced by a variety of factors. These include
a- the number of fibers within the muscle that are stimulated to contract.
b- the frequency of stimulation.
c- the thickness of each muscle fiber (thicker fibers have more myofibrils and thus can exert more power).
d- the initial length of the muscle fibers when they are at rest. It means the adding together of individual twitch contractions to increase the intensity of overall contraction. Because the contractile mechanism has no refractory period, repeated stimulation (i.e. increase the frequency) before relaxation can produce additional activation of the contractile elements and a response will be added to that already present, this is called "summation of contraction". It depends on the frequency of stimulation it occurs in 2 ways:
1 – Multiple fiber summation (increasing the number of motor units contracting at the same time).When the central nervous system sends a weak signal to contract a muscle, the smaller motor units of the muscle may be stimulated in preference to the larger motor units. Then, as the strength of the signal increases, larger and larger motor units begin to be excited as well.
2- Frequency summation and tetanization, with rapid repeated stimulation, activation of the contractile mechanism occurs repeatedly before any relaxation occurs and the response fuses into one continuous contraction and the whole contraction appears to be smooth called Tetanus (by increasing the frequency of contraction).
During tetanus the tension developed is 4 times than the individual contraction.
At slightly higher frequencies, the strength of the muscle contraction reaches maximum, so any additional increase in frequency beyond that point has no further effect in increasing the force of contraction, this is because enough Ca ions are maintained in the sarcoplasm ,even between action potentials so will not allow relaxation to happen.
But if a lower frequency is used, there will be a period of incomplete relaxation between the summated stimuli; this condition is called incomplete tetanization or clonus.