In part one of this article we discussed the history of resistance training and some very basic principles at work during adaptation to resistance training. Specificity was outlined as a governing principle with which we can predict the outcomes of our training. Low volume/high load training produce increases in neuromuscular efficiency and motor unit recruitment, while high volume/moderate load training produces only moderate increases in strength and neuromuscular adaptations along with marked hypertrophy of both slow and fast twitch fibers. Also discussed were issues such as rational and irrational adaptation. Dramatic increases in sarcomere volume without increases in myo-nuclear number, seen during irrational adaptation, effectively inhibits further increases in the production of contractile proteins and diminishes recovery and performance. Slower increases in sarcomere volume, as seen in rational adaptation, actually facilitates recovery and leads to a more steady increase in both size and strength. In part two we will discuss the mechanisms responsible for the specific nature of adaptation and look at ways of applying this knowledge to build size and strength.
To most people, the way to get a muscle to grow larger is simply a matter of “exercising” the muscle you want to grow. This is a very simplistic way of looking at it. Those individuals who fail to realize that there is a right way and a wrong way to train a muscle never go on to develop out of the ordinary physiques. Don’t get me wrong, the knowledge of how muscle tissue grows in response to training is not a requirement to be a successful bodybuilder. Anabolics have become the ultimate “cheat sheet”. They effectively reduce the overload threshold necessary for compensatory hypertrophy and elevate the genetic limit or plateau. If you chose not to use potent synthetic hormones you are in for a much more difficult road, and a good understanding of muscle hypertrophy will be invaluable to you as you train over the years.
At the very foundation of muscle hypertrophy is load induced tissue strain. Muscle tissue must undergo mechanical strain in order to begin the biochemical steps necessary for adaptive growth (Clarke,1996). This “strain” induced by the loading of the tissue leads to sarcolemma microtrauma. The wounding of the muscle cell after training is characterized by myofibrillar disruption, Z line smearing, discontinuity of sarcomeres and an increase in the porosity, or permeability, of the sarcolemma. The effect or result of this nonfatal cellular damage is the production, and release of growth factors that then interact with the damaged cell itself and also very importantly, with satellite cells.
Satellite cells are myogenic stem cells that serve to assist postnatal growth and regeneration in adult skeletal muscle. Following proliferation (reproduction) and subsequent differentiation (to become a specific type of cell), these satellite cells will fuse with one another or with the adjacent damaged muscle fiber, thereby increasing myonuclei numbers for fiber growth and repair. Proliferation is necessary in order to meet the needs of thousands of muscle cells all potentially requiring additional nuclei. Differentiation is necessary in order for the new nucleus to behave as a nucleus of muscle origin. In order to better understand what is physically happening between satellite cells and muscle cells, try to picture 2 oil droplets floating on water. The two droplets represent a muscle cell and a satellite cell. Because the lipid bilayer of cells are hydrophobic just like common oil droplets, when brought into proximity to one another in an aqueous environment, they will come into contact for a moment and then fuse together to form one larger oil droplet. Now whatever (i.e. nuclei) was dissolved within one droplet will then mix with the contents of the other droplet. This is a simplified model of how satellite cells donate nuclei to existing muscle cells.
There appears to be a finite limit placed on the cytoplasmic/nuclear ratio (Rosenblatt,1994). Whenever a muscle grows in response to functional overload there is a positive correlation between the increase in the number of myonuclei and the increase in fiber cross sectional area (CSA). When satellite cells are prohibited from donating viable nuclei, overloaded muscle will not grow (Rosenblatt,1992; Phelan,1997). It is not a stretch to say that satellite cell activity is a required step, or prerequisite, in compensatory muscle hypertrophy, for without it, a muscle simply cannot significantly increase total protein content nor CSA.
Some factors which regulate this process are exercise, trauma, passive stretch, massage, innervation, and the activity of soluble growth factors. Three classes of growth factors in particular have been studied extensively with respect to their effects on satellite cell proliferation and differentiation in vitro. They are; fibroblast growth factors (FGF), insulin-like growth factors (IGF), and the transforming growth factor-beta superfamily (TGF-beta). When administered in combination, these factors can induce satellite cell activities in vitro which mimic those typical of satellite cells found in vivo in growing, regenerating, or healthy mature muscle. In essence they can mimic the effects of loading without any microtrauma actually being done.
FGF is one growth factor being actively studied. Recent studies have shown that an increase in the permeability of the sarcolemma is necessary for the release of fibroblast growth factor (FGF). This is because FGF does not contain a signal transduction peptide sequence (Abraham,1986) and thus does not exit the source cell through vesicle mediated exocytosis. This “signal transduction peptide sequence” is necessary for the protein to be incorporated into intracellular vesicles and actively transported to the cell surface, and then ultimately released. Instead, it must be able to pass directly through the phospholipid bilayer of the wounded sarcomere in order to have an autocrine and paracrine effect on target tissues. This is accomplished in adult muscle fibers by inflicting microtrauma.
FGF, specifically FGF-beta, has been shown to stimulate proliferation but suppress differentiation of myogenic stem cells. This has the result of increasing the availability of satellite cells but reduces the number of them that are actively fusing with nearby muscle cells. In a study where FGF was injected directly into healthy muscle tissue, it had the effect of increasing muscle DNA content and IGF-1 peptides, but had no significant effect on total protein content or gross muscle weight (Adams,1998). These researchers speculate that the increase in DNA content was the result of increased satellite cell number. The fact that FGF was unable to induce hypertrophy reflects the fact that FGF inhibits satellite cell differentiation (i.e. the satellite cells never actually became of the muscle cell type) preventing the nuclei from producing muscle specific proteins and thereby short circuiting a critical step the growth process. An additional study involving both local injection and local implantation of FGF pellets into “regenerating”, or damaged muscle, failed to show any effect of FGF on the ability of muscle tissue to regenerate after microtrauma (Mitchell,1996). In this study FGF did have the effect of enhancing satellite cell proliferation as well as angiogenesis (capillary formation) nevertheless, it appears that FGF is not the limiting factor in compensatory muscle hypertrophy.
Insulin-like growth factor (specifically IGF-1) stimulates both proliferation and differentiation in an autocrine-paracrine manner, although it induces differentiation to a much greater degree. IGF-1, when injected locally, increases satellite cell activity, muscle DNA, muscle protein content, muscle weight and muscle cross sectional area (Adams,1998). As discussed earlier, the proliferation and differentiation of satellite cells is critical part of compensatory hypertrophy. The importance of IGF-1 lies in the fact that all of its apparent functions act to induce muscle growth with or without overload although it really shines as a growth promoter when combined with physical loading of the muscle.
IGF-1 also acts as an endocrine growth factor having an anabolic effect on distant tissues once released into the blood stream by the liver. In human volunteers, detailed information on the effect of IGF-1 on protein synthesis, degradation and balance has been obtained by using the arteriovenous difference of labeled and unlabeled phenylalanine across the forearm (Barrett & Gelfand 1989). In the aforementioned studies, “systemic” IGF-1 infusion for 6 h caused positive amino acid balance, both by inhibiting protein degradation and stimulating protein synthesis (Fryburg, 1994). This differs from the effect of peptide “hormones” such as insulin, which does not stimulate synthesis in adults (Bennet et al. 1990, Fryburg 1990, Gelfand & Barrett 1987, McNurlan, 1994). Therefore IGF-1 possesses the insulin-like property of inhibiting degradation, but in addition can stimulate protein synthesis (Fryburg 1991). The insulin-like effects are probably due to the similarity of the signaling pathways between insulin and IGF-1 following ligand binding at the receptors (Schumacher 1991, Gual 1998).
The ability of IGF-I to stimulate protein synthesis resembles the action of GH, which was shown in separate studies on volunteers to stimulate protein synthesis without affecting protein degradation (Fryburg et al. 1991, Fryburg and Barrett 1993). Although it is often believed that the effects of GH are mediated through IGF-1, this cannot be the case entirely. First, the effects of the two hormones were different, in that GH did not change protein degradation. Second, the effect of GH was observed with little or no change in systemic IGF-1 and GH concentrations because the GH was infused directly into the brachial artery (Fryburg et al. 1991).
Transforming growth factor-beta (TGF-beta) slightly depresses proliferation but inhibits differentiation. So although it is called a growth factor, it is an “inhibitory” factor involved in muscle growth. For example, one TGF-beta member known as growth/differentiation factor-8 (GDF-8), was found to have profound effects on muscle growth (McPherron & Lawler,1997). GDF-8 was found to exist in many muscles throughout the body. In order to identify the function of this protein, researchers “targeted”, or “knocked out” the gene responsible for producing it. The result was nothing less than miraculous. The mice who lacked the gene went on to grow muscles up to 3 times larger than normal mice. This is a 300% increase in muscle weight with no specific exercise or mechanical loading! You may remember pictures of these mice published in issue number 188 in MuscleMag International (MuscleMag,1998). The increase in the mass of the “mutant” mice muscles was a result of both increased hypertrophy and hyperplasia (an increase in fiber number). There are also naturally occurring mutations to this gene that result in “double muscling” of animals such as livestock. Two breeds of cattle known as Belgian Blue and Piedmontese exhibit naturally occurring mutations on the myostatin gene (McPherron & Lee,1997). This changes the amino acid sequence of the GDF-8 peptide and greatly attenuates its physiological activity.
All of these growth factors are brought into play in human models of compensatory hypertrophy. In summary, resistance exercise of sufficient load and volume causes microtrauma to the sarcolemma which increases the release and production of growth factors. This is done through increased permeability of the wounded cell membrane allowing soluble growth factors to “leak” out into the intercellular space. The growth factors then go on to increase the number, or “proliferation” of satellite cells, also called myogenic stem cells. This is done through interaction with growth factor receptors on the surface of these cells. These growth factors then go further to induce the conversion, or “differentiation” of these undifferentiated cells into cells expressing DNA of muscle origin. Once these satellite cells have undergone differentiation they can then fuse to existing muscle cells. This fusion allows the satellite cell to donate needed myonuclei to the wounded or developing muscle cell. The effect of increasing the number of nuclei within a cell allows for increased protein synthesis and ultimately hypertrophy. As mentioned earlier, there is a nuclear to cytoplasmic ratio, or “nuclear domain”, that is closely regulated by the cell. If the muscle cell is prevented from increasing the number of nuclei, it does not grow in response to overload (Phelan,1997).
All of the aforementioned processes occur with or without systemic hormonal influence or nutritional abundance (Borer,1995). In this way the hypertrophic response can be limited to the overloaded tissue. I do not mean to imply that exercise induced growth is not effected by systemic hormones and/or nutritional abundance, only that mechanisms are in place that allow for growth in localized muscle tissue in the absence of endocrine support and adequate nutritional status.
The foundation for the development of strength is neuromuscular in nature. Increases in strength from resistance exercise has been attributed to several neural adaptations including altered recruitment patterns, rate coding, motor unit synchronization, reflex potentiation, prime mover antagonist activity, and prime mover agonist activity. Aside from incremental changes in the number of contractile filaments, voluntary force production is largely a matter of “activating” motor units. In order to ascertain the relative contribution of each of these mechanisms, various measurement techniques have been utilized. Hereafter we will briefly discuss each of these mechanisms as they relate to resistance training.
Recruitment of motor units can be measured with Electromyography (EMG). As a muscle contracts, the electrical signal initiated by the motor nerve can be detected with EMG. The intensity or magnitude of this signal is sometimes described as “neural drive”. In order to explain increases in strength from resistance exercise, researchers have measured the changes in EMG activity in weight training subjects.
Hakkinen and co-workers have shown that there is an increase in EMG activity with strength training as well as a decrease in EMG activity upon cessation of training (Hakkinen,1983). Fourteen male subjects (20-30 yr) accustomed to weight training went through progressive strength training of combined concentric and eccentric contractions three times per week for 16 wk. The active training period was followed by an eight week detraining period. The training program consisted mainly of dynamic exercises for leg extensors with the loads of 80-120% of one maximum concentric repetition (1RM). Significant improvements in muscle function were observed in early conditioning; however, the increase in maximal force during the very late training period was greatly limited. Marked improvements in muscle strength were accompanied by significant increases in the neural activation (EMG) of the leg extensor muscles. The relationship between EMG and high absolute forces changed during the training period. The occurrence of these changes varied during the course of training. During detraining, there was a decline in EMG activity.
Now those who would argue that increases in strength are solely due to increased recruitment of motor units would have a difficult time defending themselves in light of other research. The is a method of measuring motor unit activity called “Interpolated Twitch Technique”, or ITT. ITT is used to determine the extent of activation of the entire muscle. Merton (Merton, 1954) was the first to use this technique to describe whole muscle activation. He showed full activation of the adductor pollicis with fatigue in untrained subjects. Several other studies have since shown a similar ability of untrained subjects to voluntarily fully activate various muscle groups (Bellemare 1983, Chapman 1985, Gandevia 1988, Belanger 1981). This directly contradicts the theory of strength increases due to the ability to activate more motor units.
The activation of motor units is done in an asynchronous fashion, meaning that not all fibers contract at the same time within a given muscle. There is a hierarchy to the order of fiber recruitment in muscle tissue. Because fiber activation is not “analog” or variable in nature, in other words, a fiber is either fully activated or fully quiescent, the brain must control contraction intensity by altering the number of fibers it activates. In general, slow twitch fibers are activated first followed by larger fast twitch fibers. Now when muscles begin to fatigue the asynchronous firing of fibers become more and more synchronized (Butchal, 1950). This allows for greater force production. This synchronization of muscle fibers has been linked to increases in voluntary strength (Milner-Brown, 1975). Now although increases in motor unit synchronization have been reported with training, studies involving artificial stimulation show that force development with asynchronous stimulation is greater and smoother (Clamann, 1988). In addition, researchers have shown that the rate of force development in brief maximal contractions is faster in voluntary than in evoked contractions (Miller, 1981). So from these studies we see that although synchronization of motor units can increase with training, asynchronous motor unit activation is more advantageous to rate and magnitude of force development than is synchronous activation.
Increases in “reflex potentiation” have also been linked to resistance training (Sale & Upton 1983, Sale & MacDougall 1983) as well as decreases with immobilization (Sale, 1982). The actual benefit, if any, of this adaptation is unclear. An increase in reflex potentiation would contribute to the voluntary EMG signal augmenting the motor or neuronal drive. Nevertheless, because untrained individuals have been shown to be able to fully recruit their motor units, the purpose of increased reflex potential remains undecided.
Finally, that activity of prime mover agonists and antagonists plays a role in directed voluntary strength. The obvious role of agonists is to assist the prime mover by guidance and stabilization. This could be termed “coordination”. It is well known that any unaccustomed exercise requires practice in order to develop sufficient coordination to allow maximum efficiency of muscular effort. The role of antagonistic muscle groups is more complicated. They serve to prevent damage through co-contraction as well as ensure less resistance through relaxation to prime mover contractility.
The protective mechanisms function by way of golgi tendon organs (GTO). The GTO is sensitive to force output or tension within the muscle. They are located at the musculo-tendonous junction and is contained within a compressible collagenous capsule. Fibers of the GTO are connected directly to muscle fibers as well as to Type “Ib” inhibitory neurons within the muscle. The physical structure of the GTO allows it to be sensitive to stretch or load present in the muscle. Think of the notorious “Chinese finger trap”. You first stick you fingers in each end. Then as you pull your fingers apart, the structure of the woven tube causes it shrink (or in the case of GTO it compresses) in diameter in order to stretch. The GTO works very much like this. When the collagen around the GTO is compressed because of contraction or stretch by the muscle, the Ib neurons generate an impulse that is proportional to the amount of GTO deformation. In this way the GTO can decrease contraction of a muscle being stretched in order to protect it from being torn. Likewise, GTO are thought to prevent unusually high contractions of a muscle in order to protect it from tearing itself apart. So in an antagonist muscle, the GTO can serve to inhibit co-contraction, facilitating contraction of the prime mover. In a prime mover, the GTO acts to prevent torn pecs, biceps and whatever else you are using to lift insanely heavy weights.
Another neuronal structure regulating involuntary muscle activity is the muscle spindle. The muscle spindle is found in greater abundance in the muscle belly as apposed to the musculotendonous junction. The muscle spindle also responds to stretch. However, the spindle is less like a Chinese finger trap and more like spring. When the muscle undergoes stretch, the center of the spindle is stretched. These spindles contain neurons that are sensitive to this stretching. Unlike with the GTO, when a muscle spindle is stretched its excitatory neurons fire in order to counteract the stretch. When a stretch is imposed on a muscle, the Type-I sensory neuron sends impulses into the spinal cord and connects with interneurons, generating an excitatory local-graded potential that is sent back to the muscle being stretched. If the stretch is of sufficient magnitude and/or rate, a local graded impulse will be sent back to the same muscle with sufficient strength to initiate a contraction via alpha motoneurons. This reflex arc in known as the “stretch-reflex” and is characterized by a quick muscular contraction following a rapid stretch of the same muscle. Now this stretch reflex primarily functions in slow twitch muscle fibers.
Alterations in the sensitivity of these two regulatory mechanisms have been seen with training. Carolan (Carolan, 1992) showed a decrease in antagonist co-activation of the lex extensors with training. On the other hand, increases in co-activation have been seen in longitudinal studies comparing explosive trained athletes to non-explosive trained athletes (Osternig 1986, Barrata 1988). These somewhat contradictory results may reflect the possibility that co-activation alterations are very specific in nature and depend on things such as contraction velocity, range of motion, and training specific effects.
Of primary interest to bodybuilders is training for size. After all, what is bodybuilding but doing whatever you can to make your muscles larger. The goal now is to use the current knowledge of the way muscle tissue reacts to imposed mechanical overload and microtrauma to plan a training strategy or routine that best elicits a growth effect. Understand that from here on out you are going to see areas where different approaches would be equally valid. One reason for this is the lack of quality research looking specifically at muscle hypertrophy in humans using typical (or atypical for that matter) exercise protocols that last for more than 8-12 weeks. In part 1 of this article we mentioned the fact that the length of a standard school semester or quarter usually dictate the length of a given study. Volunteers are hard to keep track of when their schedules change or when summer starts.
Thus far in Part II we have discussed the various mechanisms by which muscle adapts to resistance exercise. This is very important to understand if we are going to make advances in training techniques and planning. We know that in order for a muscle to undergo compensatory hypertrophy it must be subjected to sufficient trauma to activate satellite cells. This is done through the activity of various growth factors which all act in concert to regulate muscle hypertrophy. We also know that in order to increase our strength we must increase the “efficiency” of nerve conduction and motor unit coordination. Training to accomplish this relies heavily upon the principle of specificity which was spoken of in Part 1 of “Advanced Training Planning for Bodybuilders”. If you simply want brute force you must train the nervous system and the resultant increase in strength will reflect the manner in which you trained. Now one should not assume that training for size will automatically lead to significant increases in size. This simply isn’t true. In Part 3 we will examine specifically what methods can be adopted to cause increases in muscle size or increases in muscular strength. You might be surprised with what we come up with so stay tuned.
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