In this article we will discuss about:- 1. Composition of Skeletal Muscles 2. Properties of Skeletal Muscles 3. Vascular Arrangement 4. Rate of Blood Flow 5. Control of Skeletal Muscle Blood Flow 6. Contractions.
Composition of Skeletal Muscles:
Skeletal Muscles Composition:
i. Water—75%
ii. Solid-25%
Solids:
1. Proteins:
20%. Actin and myosin form about half the total muscle protein. Myosin, actin and their complex actomyosin, tropomyosin A (purified) and B (native or Bailey’s tropomyosin or metin), troponin, α-actinin, β-actinin and M-band filament (nature of the latter protein is not known) have been isolated. Proteolytic enzymes break myosin into light meromyosin (straight helical body portion) and heavy meromyosin (head portion).
This heavy meromyosin can again be divided into heavy meromyosin sub-fragment II (neck portion) and heavy meromyosin sub-fragment I (proper head portion) that contains the ATP-ase activity of the myosin. Actin may be of G-actin or F-actin form. Actin also contains tropomyosin and troponin. Actomyosin is a complex of three myosin and one actin. Tropomyosin B (native) contains tropomyosin A and troponin.
Tropomyosin and α-actinin are found at the Z-disc. Myogen is a protein of albumin nature and can be differentiated as myosin A and B. Enzymatic property is attributed to myosin A fraction. Myoalbumin is another protein found in sarcoplasm. Myoglobin is a conjugated protein and also named as muscle haemoglobin.
Though it is functionally similar, still it differs from blood haemoglobin by molecular weight, isoelectric pH and absorption bands. The iron content is same in both cases. Several other proteins over and above the names already mentioned, are obtained in muscles in small amounts which are component-C, delta protein, metamyosin, contractin, X-protein and Y-protein. Little is known regarding their nature, properties and functions.
2. Fats:
0.2% including cholesterol, leicithin and neutral fat.
3. Carbohydrates:
1.0%.
(a) Glycogen 0.5-1.0%.
(b) Hexose phosphate-0.05%.
4. Inorganic Salts:
1.0-1.5%. Contains potassium phosphate mainly, (K about 0.3%) and also traces of Ca (0.007%), Na (0.06%), Mg (0.02%). Fe, CI (0.04%) and sulphate. Phosphates remain in various forms (P-0.2%). The ratio between Na: K is 1: 5.
5. Extractives:
i. Non-Nitrogenous:
a. Lactic Acid -0.02% in fresh resting muscle.
b. Inositol- (muscle sugar, hexahydroxycyclohexane): 0.25%.
ii. Nitrogenous:
a. Adenosine Triphosphate (ATP):
0.25%. Adenosine diphosphate (ADP). Adenylic acid—also called Adenosine monophoshate (AMP): 0.15%.
b. Creatine Phosphate (CrPO4):
Phosphocreatine or phosphagen—0.5%. (Creatine 0.35%).
These phosphoric acid compounds act as coenzymes by working alternately as donors and acceptors of phosphoric acid. They form an essential part in the processes of phosphorylation involved in the chemical reactions underlying muscular contraction.
c. Xanthine, Hypoxanthine and Inosinic Acid:
Derived from adenylic acid of the tissues and the nucleoprotein of the nuclei.
d. Carnosine:
0.3%. It is a dipeptide (B-alanyl histidine). In some animals its methyl derivative is found and is called anserine.
6. Pigments: (Porphyrin Derivatives):
i. Myoglobin (Myohaemoglobin or Myochrome):
It is an iron-containing chromoprotein found in red muscles.
ii. Cytochrome (Myohaematin):
It is an iron-porphyrin pigment, found in three forms—a, b, c.
iii. Flavines and others.
7. Enzymes and Coenzymes:
i. Enzymes and coenzymes of the glycolytic cycle.
ii. Those that break down and re-synthesize ATP and phosphagen.
iii. Enzymes of the citric acid cycle that finally oxidize pyruvic acid into CO2 and H2O.
iv. Other enzymes like deaminase, etc.
Properties of Skeletal Muscles:
1. Excitability and Contractility:
With an adequate stimulus, muscles are excitable. The stimulus may be mechanical, thermal, chemical or electrical. For facilities of accurate adjustment, electrical stimulus is used in laboratory experiments.
When excited, the muscle contracts. This is immediately followed by relaxation. A single induction shock will produce a single contraction (twitch). The record of this on a moving drum (Fig. 6.1) will produce a curve, called the simple muscle curve (Fig. 6.2). But if the stimulus be strong, it may cause stronger contraction.
Simple Muscle Curve:
The simple muscle curve (Fig. 6.2), as obtained with a frog’s gastrocnemius, has a total duration of about 0.1 second.
It consists of three parts:
i. Latent period (0.01 second). It is the interval between the application of stimulus and the beginning of contraction.
Latent period is due to time taken:
a. For propagation of impulse from the point of stimulation to the neuromuscular junction and thence to the sarcolemma, and
b. For initiation of contraction.
ii. Period of contraction (0.04 second), from beginning of the contraction up to the maximum contraction.
iii. Period of relaxation (0.05 second), from the summit up to the original level.
Effects of salts and ions:
(a) Sodium salts exert an excitatory effect,
(b) Calcium salts have got role in initiation of contraction. Development of tension of the muscle is prevented if the Ca++ is not present in the medium. It is claimed that the Ca++ stimulates ATP-ase activity so that the association of lactin and myosin in presence of ATP takes place promptly. Calcium ions and to a less extent Mg ions help the enzyme action of myosin.
(c) Potassium salts reduce excitability and hasten fatigue. On stimulation, potassium ions escape from the interior of the muscle. It is believed that the excitability, contractility and electrical phenomenon of the muscle depend largely upon this migration of the potassium ions. The resting muscle membrane is permeable to potassium ion but not to sodium ion.
(d) Magnesium ion is essential for the action of the enzyme phosphorylase which is very important for the phosphate transfer during muscular contraction, and
(e) Increased H-ion changes exert the same effect as excess potassium.
2. Refractory Period:
After stimulation there is a brief period during which the muscle is not excitable to a second stimulus. This period is called refractory period. In the case of smooth muscles, refractory period is very short and falls within the latent period. In the skeletal muscles of frog, it is about 0.005 second, in the mammalian muscles it is about 0.002 second. Cold lengthens and heat shortens this period.
During the first part of the refractory period, the muscle remains in-excitable to any strength of stimulus and is known as absolute refractory period. But in latter part of the refractory period the muscle may be excitable only with a stronger stimulus, and is known as relative refractory period. The absolute refractory period in skeletal muscle is shorter than in cardiac muscle and for this reason the skeletal muscle can be tetanised or fatigued.
The earliest chemical change during muscular contraction is the breakdown of adenosine triphosphate (ATP). So long as the broken ATP is not re-synthesised in adequate amounts, the muscle cannot be excited. Refractory period is that period during which this re-synthesis of broken ATP takes place.
3. Tonicity:
In the body the skeletal muscles always remain in a state of light tension. This is called tone. Tone of the skeletal muscle may be defined as the reflex sustained and partial contraction. In isolated muscle, tone is absent. If the motor nerve of the muscle is excised, tone is also lost. These experiments show that muscle tone is a reflex process, the centres being situated in the spinal cord.
A muscle under tone does not show fatigue. This is due to the fact that in tone production, the whole muscle is not contracting simultaneously. Only a few muscle fibres are contracting at a time. The muscle fibres contract in batches. When one batch is contracting, the other is relaxing. Hence, the whole muscle does not show any fatigue.
4. Conductivity:
After simulation the wave of contraction starts at the point of stimulus and is propagated both ways along the muscle. In frog’s muscles the rate of propagation is 3-4 metres per second. In warm-blooded animals 6-12 metres per second.
5. Extensibility and Elasticity:
Muscle extends when stretched. When the tension is released, it goes back to its original length. But this elastic return is a little slower. A rubber band is found to extend uniformly by increasing loads of equal weights upon it and returns quickly to the original position as soon as the weights are removed. But under the same conditions, muscle does not immediately come back to its original position. It takes a little longer time. This is called extension remainder.
Vascular Arrangement in Skeletal Muscle:
Blood vessels and also nerves enter the muscle at neuromuscular hilus, which is often located, at the half length of the muscle. Arteries, after entering the substance of the muscle, branch freely ‘along the perimysium and forms numerous anastomoses, small arteries are given off at regular interval from this network and again finer arteries come out and cause free anastomosis of secondary cubical network.
From the threads of the secondary network, smallest arteries or terminal arterioles generally branch off transversely to the long axis of the muscle fibre and at fairly regular intervals of 1 mm. Finally, these arterioles open up into capillary network that runs parallel to the long axis of the muscle fibre and with frequent transverse linkages forming a delicate oblong mesh. The venules are intercalated regularly between arterioles and follow almost exactly the course of arterioles and arteries. The veins have got valves which direct the blood to flow towards the heart.
The muscles usually possess a rich capillary blood supply. A large man having a muscle mass of 50 Kg, possesses about 2,000 capillaries/mm2. Total length of the capillary of such muscle will be 100,000 Km (62,000 miles). Krogh (1929) has described that during rest approximately 100 capillaries/mm2 remain open but during exercise as 3,000 capillaries/mm2 are open up (Fig. 7.113).
Muscle blood vessels are comprised of large elastic vessels which may convert the pulsatile flow into smooth steady flow. Gollenhofen (1968) has described a spontaneous fluctuation in muscle blood flow even in nesting state.
There are two sets of resistance vessels; one is the pre-capillary, mostly the arterioles and other is the post-capillary which are mainly small veins. These vessels actually offer the major resistance to blood flow. There are capacitances vessels which are the veins and have little effect on resistance but have got influence on cardiac output.
Arteriovenous anastomosis is present in skeletal muscle. Microscopic studies on the circulation of rat skeletal muscle show many arteriovenous communications. In resting state most of the flow is through these anastomoses and to the muscle fibres proper. Functional importance of arteriovenous anastomosis is not clear.
Rate of Blood Flow through Skeletal Muscle:
Resting muscle blood flow is about 7-9 ml/100 gm tissue. During exercise, the blood flow is tremendously increased. It may be increased more than 100 ml/100 gm tissue. During exercise nearly all the capillaries are open up and for this reason the flow is increased. During rest, only 3-4% capillaries remain open.
During rhythmic muscle contraction, the steady blood flow to the muscle is greatly affected and flow becomes intermittent, i.e., flow increases during relaxation and decreases during contraction. The cause of decreased blood flow during contraction is due to compression of blood vessels.
Basal Tone of Arterioles:
In resting state, muscle blood vessels, particularly the arterioles, exhibit a tremendous basal vasomotor tone as indicated by 80-90% decrease of vascular resistance following intra-arterial administration of acetylcholine. This basal tone is considered to be due to sympathetic supply to muscle. Because blocking of the sympathetic nerves may reduce the vascular resistance.
Control of Skeletal Muscle Blood Flow:
i. Auto-Regulation of Blood Flow:
In isolated and denervated muscle preparation, blood vessels exhibit good auto-regulation when perfused at controlled arterial pressure. Jones and Berne (1965) have described that equilibrium value of blood flow following a change in arterial pressure, venous pressure or ambient pressure appears to result from a response of the resistance vessels, based on metabolic rather than myogenic mechanism.
The tremendous increase of blood flow that occurs following onset of exercise is presumably due to local vasodilatation of arterioles. It has been described that during exercise, skeletal muscle exhibits local auto-regulation which is probably due to local increased need of O2. Berne (1963, 1968) has described a metabolic regulation of blood flow in relation to O2 need of the cardiac muscle.
He has described that blood flow in the muscle is metabolically controlled when the O2 content of the venous blood is decreased. This increased blood flow takes place during such condition through reactive hyperaemia. However Berne in 1968 did not consider the adenosine to be the chemical agent responsible for active hyperaemia in skeletal muscle. Whether any related substances are involved, is not clear.
ii. Nervous Control:
In skeletal muscle, the sympathetic nerve has got dual functions. It has got vasoconstrictor and vasodilator function. The blood vessels receive both sympathetic adrenergic vasoconstrictor fibre and sympathetic cholinergic vasodilator fibre. The vasoconstrictor fibres when stimulated cause profound decrease of blood flow through the liberation of noradrenaline.
This vasoconstrictor effect has got some physiological importance because during shock or in other conditions of stress, when blood pressure falls greatly, peripheral vasoconstriction may improve the blood flow of the vital organs (brain and heart) by curtailing the blood flow of the muscle bed.
In certain condition, epinephrine may indirectly cause vasodilatation through the activation of metabolic regulation of blood flow as in case of exercise.
Sympathetic cholinergic vasodilator fibres often cause vasodilatation by the liberation of acetylcholine at their nerve endings when stimulated. These fibres are possibly activated under emotional stress or in fainting reaction. Forearm blood flow is increased greatly when a subject is frightened. Evidence of functional existence of parasympathetic nerve supply to the muscle is lacking.
iii. Reflex Control of Blood Flow:
The skeletal muscle blood flow is reflexly controlled under certain conditions of the body.
a. Sino-Aortic Baroreceptor Reflexes:
During systemic rise of blood pressure, the baroreceptors of carotid sinus and aortic arch are stimulated causing withdrawal of vasoconstrictor activities of the sympathetic vasoconstrictor fibres. On the contrary on withdrawal of baroreceptor activity by bilateral carotid occlusion (BCO), the vasoconstriction occurs in the muscle. This vasoconstriction may be abolished by a receptor blockades or by sympathetic nerve denervation. But this effect is unaffected by atropine.
b. Carotid and Aortic Chemoreceptor Reflexes:
During hypotension or in haemorrhage the carotid and aortic bodies are stimulated causing systemic rise of pressure by the decrease of blood flow to the muscle and splanchnic bed. If the sympathetic nerves to the muscle are cut, then this decrease of blood flow no longer occurs.
c. Thoracic Aorta Baroreceptor Reflexes:
Gruhzit and others (1953) have observed the reflex vasodilatation of the limb muscle following stimulation of the mechanoreceptors of the wall of the thoracic aorta.
d. Cardiopulmonary Receptor Reflexes:
In human beings, vasodilatation may occur only in the forearm if the lower limbs in a recumbent subject are elevated. It is the result of shifting of blood from limbs to the thorax by stimulation of the receptors in the cardiopulmonary low-pressor area, so that the sympathetic vasoconstrictor tone is altered.
Role of sympathetic vasodilator fibres on the above reflexes is not known.
iv. Neurohormones:
Acetylcholine has got dilator effects on the skeletal muscle blood vessels. Intra-arterial administration of acetylcholine has got no effect if atropine is administered previously. Adrenaline has got both vasodilator and vasoconstrictor effects because it activates both α- and β-receptors of the skeletal muscle blood vessels. Noradrenaline, on the other hand, has got only vasoconstrictor effect and activates only the a-receptors of the blood vessels.
v. Blood Gases:
If the pCO2 in the systemic blood is increased, then the muscle circulation is decreased due to reflex vasoconstriction by the activation of carotid and aortic chemoreceptors, whereas local accumulation of CO2 causes vasodilatation by reactive hyperaemia.
Local hypoxia may also produce vasodilatation by same mechanism. But the role of blood gases on the skeletal muscle blood flow is inconclusive and requires further study.
vi. Blood pH:
A decrease or an increase of pH has practically no effect in innervated muscle in the forearm blood flow. If the sympathetic nerves are blocked then an increased or decreased pH may alter the blood flow.
vii. Nucleotides:
Studies on adenosine, AMP, ADP and ATP show arteriolar vasodilatation but relative role of these substances in the skeletal muscle blood flow during reactive hyperaemia is not yet fully known.
viii. Polypeptides:
(a) Bradykinin is a potent vasodilator of skeletal muscle as evidenced from plethysmographic studies. However, the relative role of bradykinin on skeletal muscle vasodilatation is not known, and
(b) Angiotensin administered intravenously produces renal vasoconstriction and some extent the splanchnic bed resistance is increased on and muscle vascular bed remains unaffected. This effect causes marked shift of blood from the viscera to the muscle bed.
ix. Ions:
Increased blood levels of potassium and magnesium elicit arteriolar dilatation. These ions produce their effects by acting directly on the vascular smooth muscle.
x. Other Metabolites:
Citrate, acetate, pyruvate also produce arteriolar dilatation. Lactic acid also has got similar effect.
Hypoxia, increased CO2 tension, lactic acid, bradykinin, histamine, acetylcholine, adenosine triphosphate, adenylic acid and potassium ions have been considered to be the determinant of muscle circulation during exercise hyperaemia.
xi. Exercise:
Muscle blood flow during exercise has also been considered. With the onset of muscular work, the metabolic need of O2 is increased tremendously and such need is made adequately through activation of cardiovascular, respiratory and neuroendocrine processes along with local modification of muscle blood circulation. If these mechanisms fail then the anaerobic processes prevail, causing accumulation of lactic acid in the muscle and blood and ultimately leading to exhaustion or fatigue.
The blood circulation that increases during exercise is possibly due to reactive hyperaemia caused through metabolites acting directly on the vascular smooth muscle or indirectly through axon reflex. It has been considered that the hyperaemia which is produced by metabolites is mostly dependent upon combinations of several factors instead of one single factor.
In the working muscles, local changes of pH and composition of interstitial fluid cause opening up capillaries and arterioles that are not already dilated by the sympathetic vasodilator activities. Extracellular K+ concentration is so much increased during muscular exercise that this can account for a major part of the vascular dilatation accompanying muscular activity.
Contractions of Skeletal Muscles:
Characteristics of Isotonic and Isometric Contraction:
Contractions are of two types—isotonic and isometric. In isotonic contraction physical shortening of the muscle is allowed when one end of it is attached to a light weight which is lifted. This type of contraction gives simple muscle curve. In isometric contraction physical shortening of the muscle is reduced to minimum by making it contract against a strong spring. The slight change in the spring is magnified by suitable instruments and is recorded.
The curve of isometric contraction shows the following peculiarities:
(a) The latent period is longer,
(b) The period of contraction is longer and the tracing at first shows an upward concavity followed by an upward convexity up to the summit,
(c) Relaxation period is more gradual and the curve shows a gentle slope with a slight upward concavity.
The rise of tension is abrupt and commences very early. The amount of tension is also much higher than in isotonic contraction. Other things remaining constant the tension developed in the muscle fibres is directly proportional to the initial length of the fibre. The evolution of heat is also much more than in isotonic contraction.
Nature of Voluntary Contraction:
Voluntary contraction differs from simple muscle twitch in two respects. First it lasts much longer and secondly, the degree of contraction can be finely adjusted at will. The voluntary contraction is neither a simple muscle twitch nor tetanus. The rate of discharge is slow and less than fusion frequency and the number of cells discharging may vary in number and consequently the muscle fibres affected will, vary. The cells do not all discharge at the same time. But they work in ‘batches’.
While one group is discharging the other group is resting. For this reason, the muscle fibres of all the motor units are not in the same state at the same time. They are at different phases of contraction and relaxation. Their algebraic sum gives a smooth, steady pull. The accurate gradation in the strength of contraction is due to the involvement of varying number of anterior horn cells.
Contracture:
Under certain conditions skeletal muscles show a peculiar type of persistent contraction. This is called contracture.
It differs from tetanus or any other forms of physiological contraction in two ways:
First, in contracture only a part of the muscle may be involved, while the rest of the muscle remains relaxed.
Secondly, the contractile process is not propagated along the muscle fibre and also no action potentials are seen with it.
Contracture may be found under various conditions, such as:
(a) By strong, prolonged or multiple stimuli,
(b) In fatigue, and
(c) In certain pathological states of the body.