Muscle Fibre Solution
If the skinned muscle fibre is immersed in the salt solution similar to intracellular muscle cytoplasm and also contains Ca2+, the cell membrane of the fibres will become impermiable for small molecules like ATP because the permeability of the cells depend on the concentration of free ionized calcium Ca2+ in cytoplasm.
This can be explained with the help of an example. Put the whole muscle fibres in the Ca2+ indicatorfura-2 conjugated to high molecular weight dextran. Thefluorescence when measured from cytoplasm was found 17 degrees C (Isaevaand & Shirokova, 2003). The fluorescenceexcitation spectrum of fura dextran was turned slightly red in resting fibers compared with the spectrum of the Ca (2+)-free indicator inbuffer solutions.
If we compare the spectra in the cytoplasm and inthe vitro solutions, we find an apparently "negative" cytoplasm (Ca2+), which probably reflects an alteration of the indicator propertiesin the cytoplasm. To change the indicator's fluorescence signal in termsof cytoplasm [Ca2+], we applied beta-escin to permeabilize the cellmembrane of the fibers immersed in fura dextran.
After treating this fibre with 5micro M beta-escin for 30 to 35 minutes, the cell membrane becomes permeable to smallmolecules like Ca2+, ATP, etc, whereas the 10-kD fura dextran only slowlyleaked out of the fibre. Thus, it is possible to estimate calibrationparameters in the indicator fluorescence in the fibers by changing thebathing solution [Ca2+] to various levels (Watanabe & Konishi, 1995).
The other substances essential for being the muscle fibre impermeable are fura dextran, MWapproximately 10,000 and 0.52 microM.
The muscle fibre will remain permeable in absence of these substances for all kinds of substances.
Mechanism of graded skeletal muscle contraction in quadriceps:
There are many factors which are responsible for the contraction in quadriceps one of them is the force per fiber cross sectional area. Number of mitochondria which is present in the fiber plays important role in the supply of energy through the help of oxidative metabolism. With ageing cross sectional area of muscle tend to decrease due to decrease in the area of type 2 fibers and as a result of this a reflex which is termed as knee jerk reflex takes place. A specific kind of ligament namely strike patellar stretches the muscle of quadriceps and activate the sensory neuron which in turn synapses with the α-motor neuron to quadriceps and results in the contraction of quadriceps (Frueh, Hayes, Lynch & Williams, 1994, March 1).
Mechanism of graded skeletal muscle contraction in extra ocular muscle of the eye:
Movement of eyes is controlled by extra ocular muscles which are six in number and their actions depend upon the position of eye. Contraction in these muscles can be achieved by the experiment of temperature sensitivity (10-35 degrees C). Superior rectus and levator palpebrae superioris are the two muscles which show different response toward the temperature sensitivity. Superior rectus show fast contraction at 20 degree C then levtor but on the other hand produces lower maximum force level. Superior rectus show recreation phase which is biphasic in nature as a result of twitch response.
There are many antioxidants which alter the rate of skeletal muscle fatigue in different manner. Take a single fibre which is isolated from digitorum brevis of mouse. The antioxidant Tiron slowed down the rate of fatigue at 37ºC when compared to room temperature (22ºC). To measure intracellular calcium, single fibres were mixed with indo-1. A large decrease in myofibrillar Ca2+ sensitivity is responsible for the increased rate of fatigue at body temperature (37°C). The presence of Tiron is responsible for the decline of Ca2+ sensitivity and simultaneously decline in tetanic [Ca2+]i was noticed (Moopanar & Allen, 2005).
Mechanism: Single fibres were dissected from digitorium brevis muscle of mice by killing them through cervical dislocation. Single fiber and muscle bundle were fixed at the tendon location with the help of aluminium foil microclips. These microclips were affixed to a force transducer at one side and at nearest hook on the other side. Then, muscle preparations were fixed to a length which gives maximum tetanic force.You can get expert help with your essays right now. Find out more...
Solutions were superfused at either room temperature (22°C) or at 37°C with a solution containing (mm): NaCl, 121; KCl, 5.0; CaCl2, 1.8; MgCl, 0.5; NaH2PO4, 0.4; NaHCO3, 24; and glucose, 5.5. Then, the solution was bubbled with the combination of 95% O2 and 5% CO2, which results in a solution with a pH of 7.3. Probenecid was added in the concentration of 1mm to all the solutions when indo-1 was microinjected to decrease the rate of fall of indo-1 from the cell. Hence, it shows that Tiron in the concentration of 5mm did not affect the contraction of unfatigued muscle but plays an important role in the protection against the effects of high temperature when present throughout the course of fatigue (Moopanar & Allen, 2005).
Calpains inhibitor drug: It is generally used to inhibit muscle calpains which is the family of Ca2+-dependent cysteine proteases and is activated during reperfusion & ischemia. This drug is A-705253 and useful in myocardial protection. Like experiment in an ischemia/reperfusion pig show the effect of this drug (A-705253) in the context of cardioprotective study.
The left anterior descending coronary artery was first occluded for the time period of 45 mins and then reperfused for about 6 hrs. Bolus of 1 mg/kg A-705253 was given 15 mins before initiation of ischemia and a stable plasma level was obtained by regular mixture of 1mg/kg of A-705253 during the course of reperfusion. Tryphenyletrazoliyum chloride was used hisochemically to assess the infarct size. Light microscopy helps in the verification of macromorphometric results (Khalil et al., 2005).
A-705253 helps in the reduction of infarct size from 30 to 35% as compared to other drugs. A-705253 satisfies alteration in heart rate, central venous pressure, blood pressure and left atrial pressure during the course of ischemia and in the first two hrs of reperfusion. This shows that it is possible to achieve myocardial protection with the help of A-705253 as it reduced the size of infarct and improves contraction of left ventricular as well as the function of hemodynamic. Hence it can be used as cardioprotective drug because it proves itself as a effective immunization tool in the cure of reperfusion and ischemia (Khalil et al., 2005)
Earlier, it was considered that the important reason for skeletal muscle fatigue was intracellular acidosis, which happens due to lactic acid accumulation. Recent studies on mammalian muscle show that intracellular acidosis does not affect muscle function heavily at physiological temperature. Rather, inorganic phosphate is the main reason for muscle fatigue, which increases due to breakdown of creatine phosphate (CrP) (Westeblad, Allen & Lannergren, 2006).
High-intensity exercise leads to a decline in contractile function, which is known as skeletal muscle fatigue because high energy requires more aerobic capacity of the muscle cells, and enough fraction of ATP required, which comes from anaerobic metabolism. There is a causal relationship between anaerobic metabolism and muscle fatigue and some consequence(s) of anaerobic metabolism decline(s) contractile function.
Glycogen’s anaerobic breakdown results into an intracellular accumulation of inorganic acids, out of which lactic acid is most important. Lactic acid is a strong acid; it breaks down into lactate and H+. H+ (reduced pH or acidosis) is the classic cause of muscle contraction. But the recent studies show that reduced pH has little effect on muscle contraction at physiological temperatures. In addition to this, anaerobic metabolism in muscle also involves hydrosis of creatine phosphate (CrP) to creatine and inorganic phosphate (Pi). Creatine has little effect on contractile function but increased Pi may depress contractile function by several mechanisms (Westeblad, Allen & Lannergren, 2006).
Training regimes for top athletes in endurance sports emphasize “lactic acid training,” i.e., training protocols, which induce high plasma lactic acid levels. These trainings enable them to cope up with the discomfort caused by acidosis without loosing pace and technique and get the maximum effect out of muscles.
One other mechanism by which lactic acid formation may enforce a limit on performance is long-lasting types of exercise in which glycogen depletion is critical factor. The total amount of ATP produced from the stored glycogen is lower than complete aerobic breakdown because each glycosyl unit provides 3 ATP when lactic acid is made and 39 ATP when it is totally metabolized in the mitochondria to CO2 and H2O.
When muscle performance is critically depressed at low glycogen levels and because of production of lactic acid, the glycogen store is rapidly depleted. Finally, the correlation between declining pH and decreased muscle function may be coincidental rather than causal. A marked acidification implies that the energy demand exceeds the capacity of aerobic metabolism and that anaerobic pathways are used to generate ATP. It could then be that rather than acidification, some other consequence of anaerobic metabolism is the real cause of impaired muscle function, and increased Pi is a strong participant in this respect (Westeblad, Allen & Lannergren, 2006).
Duchenne muscular dystrophy is caused due to the lack of dystrophin. Dystrophin is a sarcolemma cytoskeletal protein whose deficiency leads to muscle fibre necrosis. This disease leads to severe and progressive muscle wasting and weakness. Muscles that lack dystrophin, the connection weakens and as a result of this, the sarcolemma gets subjected to the high level of tension. This leads to the partial disturbance in sarcolemma causing to the invasion of extra cellular Ca2+.
The increase in the concentration of intracellular Ca2+ triggers the degradative pathway which depends on the calcium, which causes the disruption in myofibril and muscle necrosis. However, this mechanism has not been proven definitively (Goubel & Pertuzon, 1973).
Understanding of the mechanisms responsible for muscle adaptation to varied operational need requires quantification of muscle mechanical properties. Muscle contractility and muscle elasticity were experimentally observed to be sensitive to periods of hyperactivity as well as hypo activity (Heerkens, Woittiez, Huijing & Huson, 1986).
The skeletal muscle consists of many individual muscle fibers. The muscle fibers are the basic units of muscle tissue just like the neuron is the fundamental unit of nervous tissue. More than one muscle fiber is stimulated at a time by these motor neurons and therefore a message originated from the brain often ends up by causing many muscle fibers in order for the desired effect(Glicksman, 2005).
This motor neuron plays a very vital role in the contraction of the muscle. The motor unit consists of motor neuron and the muscle fibers that are stimulated by way of releasing the neurotransmitter acetylcholine. The number of muscle fibers controlled by any given motor neuron depends on the muscle and the activity required (Glicksman, 2005).Find out how our expert essay writers can help you with your work...
The boundary between a motor neuron and muscle fiber is a specialized colligation which is known as the neuromuscular junction (Glicksman, 2005). The motor neuron releases a flood of neurotransmitters on enough stimulation that bind to postsynaptic receptors and triggers a response in the muscle fiber. The overall effect would be a decrease in knee extension and an increase in knee flexion to allow for the required posture of partially bent knees (Glicksman, 2005).
There will be an increase in the contraction of the quadriceps tendon and the posture will diminish the output of the muscle spindles which in turn will decrease the messages to the quadriceps muscle. When a muscle is stretched, sensory neurons within the muscle spindle detect the degree of stretch and send a signal to the CNS. This will also lead to weakness, slow movement, loss of dexterity and co-ordination (Glicksman, 2005). Hence, it can be said that if there is any loss in the motor neuron, it would hamper the ability of muscles to produce graded muscle contractions.
Eccentric contraction is a kind of muscle strain and it occurs when an external pressure is trying to lengthen the muscle. Hamstring strain results as a mechanism of eccentric contraction.
Mechanisms of eccentric contraction induced damage in skeletal muscle.
First mechanism: Damage in skeletal muscle as a result of eccentric contraction generally occurs in the form of muscle strengthening. All the damages are basically mechanical in nature and based on sarcoma sprain which is generally happen in muscles. Unnecessary sarcoma sprain is mainly responsible for the damage in muscle (Lieber1 & Fridén, 1999). This strain results in the mayofibrillar disruption in a step by step manner like,
Excess strain à Disruption in the Extra or Intra cellular membrane à Hydrolysis of structural protein à Mayofibrillar disruption
Irritation that results after the damage actually breakdown the tissues but prevention of it may result in to long term loss of muscle function.
Second mechanism: After eccentric contraction pain and weakness in muscles occurs as a result of the stretching. These symptoms become more sever when stretch occurs at the long muscle length. Sarcoma muscles are unstable on descending limb and it is generally proposed that unnecessary elongation of sarcoma occurs as a result of eccentric contraction on descending limb and result in reduced force. Sarcoma muscles are stabilize by cytoskeletal proteins and further damaged by activation of proteases. All of this result in disease of muscles like muscular dystrophy Proske & Morgan, 2001).
Traditionally it was said that the accretion of hydrogen ions and intracellular lactate was responsible for the weaken functioning of the contractile proteins but this phenomena was of least importance to the mammals. Another factor is the changes in the ions, failure in the release of SR Ca2+ by different mechanisms. The major cause of the fatigue has been associated with the decrease in the level of pH or acidosis.
This was observed when experiment of skinned fibre was performed under low temperature (Allen, Lamb & Westerblad, 2008). These fatigues are related to the temperature also. Apart from this, another mechanism responsible for the fatigue is the accretion of the inorganic phosphate.
Allen, D.G., Lamb, G.D. & Westerblad, H. (2008). Skeletal Muscle Fatigue: Cellular Mechanisms. Journal of Physiologic 88, 287-332. School of Medical Sciences and Bosch Institute.
Frueh, B.R., Hayes, A., Lynch, G.S. & Williams, D.A. (1994, March 1). Contractile properties and temperature sensitivity of the extraocular muscles, the levator and superior rectus, of the rabbit. Journal of Physiology 475(2), 327–336. Australia: Department of Physiology, University of Melbourne.
Glicksman, H. (2005). Wired for Much More than Sound Part IX: Run for your Life Part 2. Retrieved June 26, 2008 from http://www.arn.org/docs/glicksman/eyw_050401.htm
Goubel, F. & Pertuzon, E., (1973). Evaluation de l'élasticité du muscle in situ par une méthode de quick-release. Journal of International Physiology and Biochemistry 81, 697–707.
Heerkens, Y.F., Woittiez, R.D., Huijing, P.A. & Huson, A. (1986). Passive resistance of the human knee: The effect of immobilization. Journal of Biomedical Engineering 8, 95-104.
Isaevaand, E.V. & Shirokova, N. (2003). Metabolic Regulation of Ca2+ Release in Permeabilized Mammalian Skeletal Muscle Fibres. Journal of physiology. New Jersey: University of Medicine and Dentistry of New Jersey.
Khalil, et al. (2005, December). Calpain inhibition reduces infarct size and improves global hemodynamics. European Journal of Pharmacology, 528(1-3), 124-131.
Lieber1, R.L. & Fridén, J. (1999).Mechanisms of muscle injury after eccentric contraction. Journal of Science and Medicine in Sport 2(3), 253-265.
Moopanar, T.R. & Allen, D.G. (2005, April 1). Reactive oxygen species reduce myofibrillar Ca2+ sensitivity in fatiguing mouse skeletal muscle at 37°C. Journal of Physiology 1 (564), 189–199.
Proske, U. & Morgan, D.L. (2001). Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications. The Journal of Physiology 537 (2), 333–345
Watanabe, M. & Konishi, M. (1995). Resting cytoplasmic free Ca2+ concentration in frog skeletal muscle measured with fura-2 conjugated to high molecular weight dextran. The Journal of General Physiology 106, 1123-1150. Retrieved June 26, 2008, from http://www.jgp.org/cgi/content/abstract/106/6/1123
Westeblad, H., Allen, D.G. & Lannergren, J. (2006). Muscle Fatigue: Lactic Acid or Inorganic Phosphate the Major Cause? Journal of Physiology and Pharmacology 17. Retrieved June 25, 2008, from http://physiologyonline.physiology.org/cgi/reprint/17/1/17
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