Physiology of Muscle
Morphology of Skeletal Muscle Fiber Each muscle composed of many muscle fibers Each muscle fiber is a single cell, multinucleated cylindrical shape surrounded by cell membrane called sarcolemma its usually innervated by only one nerve ending Each of these muscle fibers is made up of smaller subunits (myofibrils). myofibrils composed of actin and myosinnucleus
Muscle fiber
Actin myofibrils
Myosin myofibrils
sarcolemma
myofibrils
Actin and myosin
The thick filament (myosin): composed of hundreds of myosin molecules, each molecule consists of 6 polypeptide chains (4 light and 2 heavy chains). 2 heavy chain wrap spirally form the tail on the end of the tail the spiral chain folded bilaterally will form the arm and the head The head of myosin molecule form the cross-bridges which bind with actin. The head of myosin molecule contains actin binding sites and 2 ATPase activity sites (to produce the energy necessary for contraction)Light chain
head
tail
2 heavy chain
The thin filament (actin): actin filaments composed of three proteins: 1-Actin contain active sits on its surface in which the cross –bridges of myosin attached 2-Tropomyosin: lie on the top active site of actin 3-Troponin: are 3 loosely bound protein subunits-Troponin I has strong affinity to actin . binds to actin so inhibit interaction between actin and myosin-Troponin C has strong affinity to Ca ion, which is necessary to initiate contraction-Troponin T has affinity for tropomyosin form troponin tropomyosin complex Active sites
actin molecule
tropomyosin
troponin
tropomyosin filament
The myosin and actin filaments partially interdigitate and thus cause the myofibrils to have alternate light and dark bands actin held in place by Z discmyosin held in place by its attachment to Z-disc by protein titinSarcomere: is the portion of myofibrils that lie between two successive Z –disc Z disk
Z disk
sarcomere
The sarcotubular system
It is composed of: a)The transverse tubules(T-tubules) originate as invaginations from cell membrane, open to the exterior thus communicating with the ECF. T-tubules help for rapid transmission of action potential. b)The sarcoplasmic reticulum: composed of: 1-Longitudinal tubules. 2-Terminal cisterns: large chambers giving the appearance of triad. It stores calcium ionsT-tubule
Sarcoplasmic reticulum
Terminal cisterna
myofibrils
T tubules
triad
Molecular mechanism of muscle contractionIn the relaxed muscle the troponin-I is tightly bound to actin; tropomyosin covers the active sites of actin thus, troponin-tropomyosin complex represent the relaxing proteins which inhibit interaction between actin and myosinWhen the Ca ion bind with troponin C this uncover the active sites of the actin. Then the activated head of myosin cross-bridges attaches to an active sites of actin, here the head automatically tilts towards the arm(power stroke ) so dragging the actin filaments along with it immediately after tilting the head released from the active site then return to its normal perpendicular direction and then it combined with new active site of actin, then the head tilts again, and the actin filament moves another step. Thus, the heads of the cross-bridges step by step walk along the actin filament, pulling the ends of two successive actin filaments toward the center of the myosin this is called “walk-along” theory
neuromuscular junction motor nerve reaches the muscle fiber, it loses its myelin and divides into a number of terminals. The axon terminal contains many small vesicles of acetylcholine. The nerve ending invaginates into a thickened, folded depression in the muscle membrane called the motor end plate . this invagination is called synaptic gutter the space between the axon terminal and the muscle fiber is called synaptic cleft (contain acetylcholinesterase that destroy acetylcholine (Ach).
Excitation- contraction coupling
1-an action potential travel along a motor nerve to its ending on muscle fiber,voltage gated calcium channels open and allow calcium ions to enter in the nerve terminal. 2-The calcium ions cause the acetylcholine vesicles to move to the neural membrane and released by exocytosis. 3-the acetylcholine open the acetylcholine- gated channels, which allows sodium ion to flow into muscle fiberAP in motor neuron
Ach released
Ach
Ach receptors
Na
Ca enter
4- Na enter inside the muscle fiber create an end plate potential (The sudden entrance of sodium ions into the muscle fiber causes the electrical potential inside the fiber to increase in the positive direction as much as 50 to 75 millivolts). Which is necessary to initiate an A.P
5-The action potential cause the sarcoplasmic reticulum to release calcium ion into myofibrils 6-The Ca ions initiates attractive force between the actin and myosin cross-bridges causing the actin filaments to slid inward among the myosin filaments .This is the contractile process which is occur by sliding filament mechanism. 7-After a fraction of a second the Ca ion are pumped back into the sarcoplasmic reticulum.this removal of Ca ion causes muscle contraction to cease
Action potential
Ca
Calcium pump
The acetylcholine then it is removed rapidly by two means: (1 )Most of the acetylcholine is destroyed by the enzyme acetylcholinesterase (2) A small amount of acetylcholine diffuses out of the synaptic space or re-uptake by process of pinocytosis
motor unit :all the muscle fibers which is innervated by a single motor nerve are called motor unitMuscles needed precise function may have only 2-3 muscle fibers in motor unit e.g laryngeal muscle.While muscle that don’t need precise function may have 100 muscle fiber in motor unit Neuromuscular junction
myofibrils
Axon branch
Motor nerve
Simple muscle twitch
The contraction of a muscle in response to a stimulus are 3 parts of a Muscle twitch latent period :The time between application of stimulus to the motor neuron and the beginning of contraction contraction period : muscle shortens & does its work relaxation period: returns to original lengthIn skeletal muscle, the refractory period is short which means that skeletal muscle can under go summation and tetanization via repeated stimulation (eg. Lifting heavy weight)
Stimulus strength and muscle contraction 1-Subthreshold stimulus does not produce an AP, and no muscle contraction occurs. 2-A threshold stimulus produces an AP and results in contraction of the muscle fiber. 3-A stronger than threshold stimulus produces an AP of the same as the threshold stimulus and same contraction. Thus, once an AP is generated, the skeletal muscle fiber contracts to produce a constant force (all or none law). Like individual muscle fiber , motor units respond in all-or-none fashion
Increasing the force of contraction
1-Multiple motor unit Summation. By increasing the number of motor units contracting at the same time.Threshold stimulus one motor unit respond
Submaximal stimuli (increasing number of motor units respond)
Maximal stimuli (all motor units respond)
Supramaximal stimuli (no other motor unit respond
2-Frequency Summation and Tetanization: by increasing the frequency of contraction. As the frequency increases, here comes a point where each new contraction occurs before the preceding one is over. As a result, the second contraction is added to the first one,so that the total strength of contraction rises progressively.When the frequency reaches a critical level, the successive contractions fuse together, and the whole muscle contraction appears to be completely smooth and continuous without relaxation This is called tetanization .
Degree of actin and myosin filaments overlaps effect on the tension developed by the contracting muscle
At a point D- at very long sarcomere length a muscle can not develop tension because there is no over lap between actin and myosin filamentsAt appoint B and C- at a sarcomere length 2 micrometer, full tension is maintained because all the cross– bridges of myosin overlapped by the actin at this length it's capable of generating maximum force of contractionAt appoint A sarcomere length less than 2 micrometer the ends of the two actin filaments begin to overlapped causing muscle tension to decrease A
B C
B
C
D
Muscle Fatigue
Prolonged and strong contraction of a muscle leads to muscle fatigue. muscle fatigue is directly proportion to the rate of depletion of muscle glycogen.Types of muscle contraction
Isometric :tension of muscle increase but do not change in length e.x when person push against the wall. Isotonic contraction: there is change in length but the tension not changed e.x lifts an objectTypes of muscle fibers
Two types fast muscle fiber (few) slow muscle fiber (hundreds). Most of body muscles are a mixture of the twoFast Fibers
(1) Large fibers and innervated by large nerve (2) Extensive sarcoplasmic reticulum for rapid release of calcium ions. (3) Large amounts of glycolytic enzymes for rapid release of energy. (4) Less blood supply and Few mitochondria because oxidative metabolism is of secondary importance. (5)easy fatigability (6) less myoglobin ,deficit of red myoglobin in fast muscle gives it the name white muscle (7)Adapted for very rapid and very strong contraction(short distance running, jumping.)Slow Fibers.
(1)Smaller fibers. And Also innervated by smaller nerve fibers. (2) More extensive blood vessel system and capillaries to supply extra amounts of oxygen. (3) Greatly increased numbers of mitochondria, to support high levels of oxidative metabolism. (4) Fibers contain large amounts of myoglobin. The myoglobin gives the slow muscle a reddish appearance and the name red muscle. (5)resist fatigue (6)Adapted for prolonged muscular activity(marathon races, postural muscles which support body against gravityMuscle Action Potential
Almost everything regarding initiation and conduction of action potentials in nerve fibers applies equally to skeletal muscle fibers, except the following differences1-Resting membrane potential: about –80 to –90 millivolts in skeletal fibers—the same as in large myelinated nerve fibers.2-Duration of action potential: 1 to 5 milliseconds in skeletal muscle—about five times as long as in large myelinated nerves3-Velocity of conduction: 3 to 5 m/sec—about 1/13the velocity of conduction in the large myelinated nerveMuscle Hypertrophy
Forceful muscular activity increases total mass of a muscle results from an Increase in the number of actin and myosin filaments Muscle atrophy Occur when a muscle remains unused for many weeks cause a decreases in muscle massRigor
when muscle fibers are completely depleted of ATP, they develop a state of extreme rigidity called rigor, here, all actin filaments bind to myosin filaments permanently in a fixed way when occur after death it is called rigor mortis,Myasthenia Gravis
it is an autoimmune disease in which the patients have developed antibodies against their own acetylcholine channels. The AP that occur in the muscle fibers are too weak to stimulate the muscle fibers and the patient dies of paralysis.Poisoning with curare(Ach receptor blocker) cause weak endplate potential, the same effect occurs with the botulinium toxin(bacterial toxin)which decreases the release of Ach by nerve terminals
Smooth muscle
Morphologysmooth muscle is unstriated, involuntary muscle Spindle shape the sarcoplasmic reticulum is poorly developed. Smooth muscle membrane contains large number of Ca ion channels which is the main ion involved in the initiation of AP in smooth muscle
There are two main types of smooth muscle I-Multi-Unit Smooth Muscle
1-non-syncytial i.e this type of smooth muscle is composed of separate smooth muscle fibers . 2-Neurogenic: controlled by external nerve supply. 3-Contraction not spread widely therefore needed for fine localized contractions (eg: ciliary muscle and iris of the eye) 4-Very sensitive to acetylcholine and noradrenalineMulti unit
II-Single-unit Smooth Muscle
Also called “unitary” or syncytial or visceral smooth muscle it means a mass of hundreds to thousands of smooth muscle fibers that contract together as a single unit. Their cell membranes are adherent to one another at multiple points called gap junction through which ions and A.P can flow freely from one muscle cell to the nexte.g gut muscle, bile ducts, ureters, uterus, and many blood vessels Unitary smooth muscleComparison of contractile unit within a smooth muscle cell with the skeletal muscle
1-The contractile proteins are actin, myosin, and tropomyosin but no troponin. Actin filaments attached to dense bodies. In between actin filaments, there are a number of myosin filaments. The interdigitation between thick and thin filaments are randomly arranged.
2-Most of the myosin filaments have “side polar” cross-bridges arranged so that the bridges on one side hinge in one direction and those on the other side hinge in the opposite direction. This allows the myosin to pull an actin filament in one direction on one side while simultaneously pulling another actin filament in the opposite direction on the other side. The value of this organization is that it allows smooth muscle cells to contract as much as 80 per cent of their length Side polar cross bridge
Comparison of Smooth Muscle contraction with skeletal muscle contraction
Contraction of smooth muscle also occur by sliding filament mechanism, the difference in contraction are: I-Although most skeletal muscles contract and relax rapidly, most smooth muscle contraction is prolonged tonic contraction, sometimes lasting hours or even days. This is due to 1-Slow Cycling of the Myosin Cross-Bridges. 2-low Energy Required to maintain the Contraction. II-Force of Muscle Contraction is greater than that of skeletal muscleIII - The role of calcium in excitation-contraction coupling 1-The main source of calcium ions is the ECF. 2-smooth muscle contain tropomyosin but it uncover the active site and does not contain troponin, in state of it the regulatory protein called calmodulin which present in cytoplasm of the cell : Calcium ions binds with calmodulin,(an abbreviation for CALcium-MODULated proteIN) this binding will cause activation of myosin light chain kinase, ( phosphorylating enzyme) hydrolyse phosphate from ATP and bind it with myosin head cause activation of myosin heads which bring about the muscle contraction. At the end of contraction, Calcium ions are pumped back again to the ECF and to the sarcoplasmic reticulum myosin phosphatase, which splits the phosphate from the myosin head then contraction stop. and causes relaxation
Neuromuscular Junctions of unitary Smooth Muscle
I-The autonomic nerve fibers that innervate smooth muscle branch diffusely on top of a sheet of muscle fibers, innervating nerves have swellings called varicosities. these varicosities release neurotransmitters into wide synaptic clefts called diffuse junctions. II-the vesicles contain acetylcholine in some fibers and norepinephrine in others.Gap junction
Neuromuscular Junctions of multiunit Smooth Muscle
Autonomic nerve
varicosities
Synaptic vesicles
the varicosities are very close to the muscle cell membrane by as little as 20 to 30 nanometers—(the same width as the synaptic cleft) These are called contact junctions
Diffuse junctions 1-visceral smooth muscle2-varicosities near smooth muscle cell3- large distance between it and cell 1-5 μm4-number of innervated cells varies widely Contact junctions 1-multi-unit smooth muscle 2- morphologicall more like skeletal muscle synaptic cleft 3- very small distance 20 nm 4- every cell is innervated
Membrane Potentials and Action Potentials in Smooth Muscle
The normal resting membrane potential is usually about -50 to -60 millivolts. Action potentials occur in unitary smooth muscle (such as visceral muscle) in one of two forms: (1)Spike Potentials. rapid depolarization followed by rapid repolarization. The smooth muscle cell membrane has more voltage-gated calcium channels but few voltage gated sodium channels .Therefore, flow of calcium ions to the interior of the fiber is mainly responsible for the action potential. (2)Action Potentials with Plateaus. Rapid depolarization followed by plateau then repolarization . Plateau is responsible for the prolonged contraction of smooth muscle, is due to the opening of slow calcium channels . Occurs in the ureter, uterusSpontaneous electrical activity and slow wave
some type of smooth muscle cell generate action potential spontaneously in absence of any stimulation, plasma membrane of these cell do not maintain constant resting potential instate they gradually depolarized until they reach the threshold potential and produce A.P fallowing repolarization ,membrane begin to depolarized again lead to rhythmical state of contractile activity these cell are pace maker cellother pace maker cell have different pattern of activity, the membrane potential go up and down due to regular variation in Na ion flow across cell membrane this is called slow wave. slow wave rhythm of the membrane potential not an action potential, but when an excitatory in put (as food in intestine), slow wave reach above threshold and A.P occur lead to muscle contraction
Excitation of smooth muscles by stretch
When visceral (unitary) smooth muscle is stretched, spontaneous action potentials usually are generated. They result from a combination of (1)the normal slow wave potentials (2) stretch open mechanosensitive ion channels lead to depolarization and contractionSmooth Muscle Contraction in Response to Local Tissue Factors.
As occurs in small vessels(arterioles, metarterioles and precapillary sphincters) it can undergoes powerful vasoconstriction or vasodilation in response to local interstitial factors and this is called autoregulation of tissue blood flow 1- Lack of oxygen in the local tissues causes vasodilatation. 2-Excess carbon dioxide causes vasodilatation. 3- Increased hydrogen ion concentration causes vasodilatation. 4-nitric oxide from endothelial cell cause local vasodilatationEffects of Hormones on Smooth Muscle Contraction
A hormone will cause contraction of smooth muscle when act on excitatory receptors while cause relaxation of smooth muscle when act on inhibitory receptors, Some hormone receptors open sodium or calcium ion channels and depolarize the membrane, Some hormone closes the sodium and calcium channels to prevent entry of these positive ions; or opening of potassium channels cause hyperpolarization and inhibition of the musclesExcitatory and Inhibitory Transmitter Substances
autonomic nerves innervating smooth muscle ,secret neurotransmitter substance which are acetylcholine and norepinephrine, but they are never secreted by the same nerve fibers. 1-Sympathetic stimulation(noradrenaline) decreases smooth muscle activity 2-Parasympathetic stimulation(acetylcholine) has opposite effects (increase tone, force and frequency of contraction) Stretch and cold produce similar effects of acetylcholine on visceral smooth muscle.Cardiac muscle is striated, branching, Involuntary have single nucleus cardiac muscle are connected by regions called intercalated discs
Intercalated discs
Intercalated disc contains
The intercalated disc is actually cell membranes that separate cardiac muscle cells from one another). contains desmosomes(provide strong mechanical union between cardiac muscle fiber) gap junctions(protein- tunnels, allow direct transmission of the depolarization from cell to cell). thus cardiac muscle act as a single unit(syncytium), in which the cardiac cells are so interconnected that when one of these cells becomes excited, the action potential spreads to all of them.Muscle fiber have typical myofibrils that contain actin and myosin filaments.(troponin and tropomyosin also present) and their organization give the striated appearance . .has a smooth sarcoplasmic reticulum(SR) but less abundant and less organized than in skeletal muscle. .myogenic (can work without nerve supply). .has rich mitochondria and blood supply, thus cardiac muscle resist fatigue
Action Potentials in Cardiac Muscle
Resting memberane potential in cardiac muscle is about -85 millivolts. After the initial spike, the membrane remains depolarized for about 0.2 second ( plateau) , followed at the end of the plateau by abrupt repolarization. 1.Depolarization: increased Na permeability (fast Na channels), 2.Plateau: increased Ca permeability (slow Ca- Na channels) 3.Repolarization: increased K permeability(K efflux).2
1
3
Refractory Period of Cardiac Muscle
Is the interval of time, during which a normal cardiac impulse can not re-excite an already excited area of cardiac muscle. The normal refractory period of the ventricle is 0.25 to 0.30 second, which is about the duration of the prolonged plateau, therefore, cardiac muscle cannot be tetanized, a condition which is fatal. There is an additional relative refractory period about 0.05 second during which the muscle can be excited by a very strong signal, this may develop ventricular fibrillation,Excitation-Contraction Coupling
The action potential spreads to the interior of the cardiac muscle fiber along the membranes of the transverse tubules. Which act on the membranes of the sarcoplasmic reticulum to cause release of calcium ions into the muscle sarcoplasm , calcium ions diffuse into the myofibrils and promote sliding of the actin and myosin filaments along one another; this produces the muscle contraction. a large quantity of extra calcium ions also diffuses from the T tubules ,without this extra calcium , the strength of cardiac muscle contraction would be reduced why?? a-the sarcoplasmic reticulum is less developed b-the T tubules have a diameter 5 times as great as that of the skeletal muscle tubules, which means a volume 25 times as greaterFrank-Starling Law:
Increase the initial length of cardiac muscle fiber (within physiological limits) will increase the force of contraction . When an extra amount of blood flows into the ventricles, the cardiac muscle itself is stretched .This in turn causes the muscle to contract with increased force because the actin and myosin filaments are brought to optimal degree of overlap for force generation