Muscle Plasticity: Response to training and detraining

Physiotherapy July 2002/vol 88/no 7

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IntroductionAll skeletal muscles have adaptivepotential, which means that they arecapable of modifying their structure inresponse to environmental changes.Physiotherapists encounter the results ofthese changes on a daily basis and arefrequently involved in promoting orpreventing the muscular response. Theenvironmental changes that may beencountered are altered patterns ofactivity, pathological processes, metabolicconditions, ageing, and drug admin-istration. As physiotherapists arefrequently involved with the use andconsequences of increased or reducedactivity, it is this area that this articleproposes to review, ie skeletal muscleresponse to training and detraining.

Muscle StructureTo understand the changes that occur inresponse to altered activity patterns, it isnecessary to know something about the

basic structure of skeletal muscle. Thecontractile elements of skeletal musclefibrils are actin and myosin. Myosin is aprotein composed of two heavy (MHC)and two light (MLC) chains, which det-ermine the nature of the mechanicalaction performed (in terms of velocity,fatigue resistance and mechanicalefficiency). At least four different myosinheavy chain isoforms are expressed inthe limb muscles of rats, ie MHC-1,MHC-2A, MHC-2X and MHC-2B. Thesingular expression of these isoformswithin a muscle fibre results in theappearance of four different fibre types:1, 2A, 2X and 2B.

In humans, only three myosin heavychain isoforms have so far beenidentified, ie no 2B has been seen. Thishas led to the recent reclassification ofhuman type 2B fibres as type 2X fibres.Table 1 gives an overview of the rel-ationship between the current myosinheavy chain classification and the earlierforms of classification for muscle fibres.Table 2 outlines the main characteristicsof skeletal muscle fibre types. Mostskeletal muscles are composed of roughlyhalf and half types 1 and 2 fibres, thelatter being divided fairly equally betweentypes 2A and 2X. There are also hybridfibres containing multiple myosin heavychain isoforms (Talmadge, 2000).Although their numbers are generallyrelatively low, they increase during myosinheavy chain fibre type transition. There isnow overwhelming evidence that musclefibres can change not only in size, but alsoin type, in response to environmentalfactors (Scott et al, 2001; Pette and Staron,1997).

The functional unit of skeletal muscle isthe motor unit, ie a single motor nerveplus all the muscle fibres it supplies. Inslow twitch motor units a motor neurone

Muscle Plasticity Response to training and detraining

Summary All skeletal muscles have adaptive potential,which means that they are capable of modifying theirstructure in response to environmental change. Increased andreduced activity are two of the common environmentalchanges that physiotherapists see in clinical practice (eg muscle training and detraining). The purpose of thisarticle is to review the literature surrounding these two areas.Although many of the adaptations that occur in muscle as aresult of increasing or reducing activity are reasonably wellunderstood, there is still no consensus as to the best wayeither to promote or to prevent these adaptations. Generalprinciples for muscle training are accepted, but quantifyingexercise prescription (eg in terms of duration, load orrepetitions) is not standardised. One of the reasons for thislack of standardisation is the individuality of each person’sresponse to exercise, some of which may be explained bygenetic factors. Recent studies have explored the effect ofthe angiotensin converting enzyme genotype on physicalperformance, with some conflicting results.

Key WordsMuscle, training, detraining,review.

by Anne Bruton

Bruton, A (2002).‘Muscle plasticity:Response to trainingand detraining’,Physiotherapy, 88, 7,398-408.


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innervates 10-180 muscle fibres, in fasttwitch 300-800 fibres. Thus although thestrength of the individual fibres is notsignificantly different, action of a fasttwitch motor unit produces a more rapidrise in tension and relatively more forcethan a slow twitch motor unit. Skeletalmuscle action involves the selectiverecruitment of slow and fast twitch fibres,depending upon the activity required(Gollnick et al, 1974).

Recruitment of motor fibres follows asequential pattern of type 1 to 2A to 2X.Type 2X fibres are thus less easilystimulated by the nervous system and soused infrequently for normal low intensityactivity. They are recruited for higherintensity, more explosive activity. It isgenerally accepted that this orderlyrecruitment of motor fibres is explainedby Henneman and colleagues’ (1974) sizeprinciple, which states that the re-cruitment of a motor unit is directlyrelated to the size of the motor neurone,so that units with smaller motor neuronesare recruited first. Evidence for thispattern of recruitment comes mainly fromnon-human studies (particularly involvingfrogs and fish), because technical prob-lems make it difficult to assess shorteningvelocity of muscle fibres in vivo in humans (Bottinelli and Reggiani, 2000).

Reduced ActivityThe literature on muscle response toreduced activity encompasses severalfields of research beyond the purelymedical. Most human studies can beplaced within four broad categories(Talmadge, 2000) looking at muscleresponse to immobility (bed rest or limbfixation), athletic detraining, neuro-muscular pathology or trauma, orweightlessness (during space travel).

Physiological adaptations to reducedactivity depend upon the nature of thereduction, eg absence of weight bearing(as in astronauts) results in muscleweakness and atrophy (Fitts et al, 2001;Edgerton et al, 1995), whereas immob-ilisation in a cast leads to resorption ofsarcomeres as an adaptation to being heldin a shortened position (St-Pierre andGardiner, 1987).

The mechanisms that regulate theexpression of the genes encoding heavychain isoforms of myosin are not wellunderstood (Gea, 1997). It is believedthat mechanical signals, ie changes in

tension, are likely to be involved in thisregulation. It seems that fast type genesare expressed ‘by default’ (Gea, 1997)and thus a decrease in activity shouldresult in a higher expression of fastmyosin heavy chain and an increase intype 2 fibres. Transitions among thedifferent types of myosin heavy chainfollow a sequential order similar to thatseen during motor unit recruitment, ieMHC-I to MHC-2A to MHC-2X in eitherdirection according to the nature of thestimulus. This model suggests that bothreduced activity and increased activitywould lead to changes in the proportionof type 1 and type 2 fibres seen in skeletalmuscles. These changes would also occurin the sequence 1-2A-2X in eitherdirection.

In animal experiments it has beenreported that unloaded muscle does showpreferential atrophy of type 1 fibres andincreased proportions of type 2 fibres(Fitts et al, 2000; Jiang et al, 1992; Maier etal, 1976; Booth and Kelson, 1973).Experimental support for extending theprinciple to humans is lacking at present.A study by Berg et al (1997) found nosignificant change in proportions of fibretype in seven normal subjects on six weeks

Table 1: Relationship of myosin heavy chain isoforms toexisting classifications of human skeletal muscle fibre types

MHC Histochemical Enzyme Contractile Morphologyisoform staining activity speed

MHC-1 Type I Slow twitch Slow Redoxidative

MHC-2A Type 2A Fast twitch Fast Whiteoxidative

MHC-2X Type 2X (B) Fast twitch Fast Whiteglycolytic

Table 2: Characteristics of human skeletal muscle fibres

Characteristic Type 1 fibre Type 2A fibre Type 2X fibre

Diameter Small Intermediate Large

Motor neurone size Small Large Large

Nerve conduction Slow Fast Fast

Contractile speed Slow Fast Fast

Fatigue resistance High Moderately high Low

Motor unit strength Low High High

Oxidative capacity High Moderately high Low

Glycolytic capacity Low High High

Capillarity Dense Dense Sparse

Myoglobin content High Intermediate Low


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bed rest. In line with previous studies,Berg et al found that mean fibre area and diameter decreased significantly (p < 0.05), and that there was a markeddecrease in maximum voluntary force.These findings support a much earlierstudy by Sargeant et al (1977), whostudied seven fracture patients in lowerlimb plaster casts for an average of 131days. Sargeant et al found that althoughthere were no changes in the numbers oftypes 1 and 2 fibres, there was significantatrophy in both. Type 1 fibres showed agreater degree of atrophy (loss of area)than type 2. Overall there was a 42%decrease in mean fibre area. MacDougall(1986), however, found greater atrophy in type 2 than type 1 fibres of tricepsbrachii after six weeks immobilisation in plaster. This latter finding may reflect differences in the pattern ofatrophy in upper and lower limb muscles.

More recent studies during space flighthave found differences in the pattern offibre atrophy for animals and humans.Rats were found to show greater atrophyin type 1 than type 2A fibres, whereashumans showed more atrophy in type 2Athan type 1 fibres (Fitts et al, 2000). Thisdifference in pattern may be related toinitial fibre size. In rats type 2A aresmaller than type 1 fibres, whereas inhumans they are larger. Edgerton and Roy (1996) have commented on theconsistent observation that the greater the pre-flight fibre size, the greater thedegree of atrophy seen after a flight.

Human studies of cast immobilityfrequently use an uninvolved limb as acontrol, which can be problematic as the uninvolved limb itself is likely to be exposed to changing stresses. Toovercome this problem, Haggmark et al(1981) per-formed repeated biopsies onthe same subjects before and after aperiod of plaster cast applicationfollowing anterior cruciate reconst-ruction. It was found that there was loss ofarea in type 1 fibres only. The changesoccurred despite the use of isometricexercises within the plaster casts.

The difference in findings of Sargeantet al and Haggmark et al may be related totheir different methodologies. Sargeant etal used uninvolved limbs as controls forcomparative purposes whereas Haggmarket al used pre-operative values as controls.The subjects of the study by Haggmark et

al were all in casts for 35 days whereasthose of Sergeant et al ranged from 53 to213 days in casts.

The subjects of Haggmark et al mayhave experienced more pain than thoseof Sargeant et al. Pain is thought to have a greater inhibitory effect upon type 1than type 2 fibres (Gydikov, 1976), so the atrophy in type 1 fibres seen in thestudy by Haggmark et al may have beencaused by pain rather than immobility.Supporting evidence for this theorycomes from a study by Mannion et al(1997) who found that the lumbarmuscles of patients with severe low backpain had higher proportions of type 2X to type 1 fibres when compared withmatched controls. However, it is notpossible to distinguish cause from effectin this study and it is possible that thepatients had atypical fibre characteristicsbefore the onset of their low back pain.

Hortobágyi et al (2000) studied 48 painfree healthy subjects and immobilisedtheir left legs for three weeks in fibreglasscasts. Proportions of type 1 fibres reducedby 9% (p < 0.05) and numbers of type 2Xfibres increased by 7%, but numbers oftype 2A fibres were not affected. In termsof area, however, all three fibre types werereduced significantly.

The variability seen across humanstudies may be as a result of differences inthe choice of muscle studied, the type and intensity of physical activity beforethe period of inactivity, or musclecontractions occurring during the periodof ‘immobility’.

Human studies are inevitably con-strained by technical and ethical consid-erations that limit the range of possibleexperiments, which makes their resultsquestionable. Taking muscle biopsies torepresent whole muscles is in itself opento question. Repeated biopsies of thesame vastus lateralis produced variationsof 15% to 20% both in fibre type and indistribution (Rose and Rothstein, 1982),and the variability found in any group ofsubjects makes generalisations difficult tosupport. Thus there is no real consensusas to whether inactivity in humansproduces preferential atrophy of onefibre type and/or changes in distributionof fibres. It is agreed, however, that ifactivity is sufficiently reduced, muscleatrophy will ensue with associated loss ofpeak force and power (Fitts et al, 2000).Table 3 provides the main factors


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Author

Anne Bruton PhD MAMCSP is a lecturer inphysiotherapy at theUniversity ofSouthampton.

This review forms part of a PhDundertaken by Anne Bruton andsupervised by Dr J H Conway andProfessor S T Holgateat the University ofSouthampton. It was funded by the South East Researchand DevelopmentDirectorate.

The article wasreceived on July 26,2001, and accepted on March 12, 2002.

Address forCorrespondence

Anne Bruton, Schoolof Health Professionsand RehabilitationSciences, University of Southampton,Highfield,Southampton SO17 1BJ.

affecting muscle atrophy (St-Pierre andGardiner, 1987).

When a muscle becomes inactive, majorchanges are initiated within it after only a few hours (Wilmore and Costill,1994). The rate of protein synthesis, the dominant characteristic of muscleatrophy, starts to decrease (Rennie et al,1983). In rodents, a protein synthesisdecrease rate of 35% has been recordedwithin hours of onset of activity leading toa net loss of muscle protein (Wilmore andCostill, 1994). Decrease in contractileprotein concentration may lead to areduction in the number of activecrossbridges per volume of muscle and hence reduced electromechanicalefficiency (Berg et al, 1997).

It is not surprising, therefore, that totalinactivity leads to rapid losses in musclestrength. Even prolonged periods ofreduced activity can lead to significantreductions in maximal voluntary con-traction (Wilmore and Costill, 1994). Thisapplies equally to athletes who stoptraining as to non-athletes who reducetheir activity. The quantification of loss inmaximal voluntary force as a result ofreduced activity varies from study to study,but there is general agreement that thegreatest losses occur within the first fewdays to two weeks. The losses within thefirst week of immobilisation can average3% to 4% per day (Appell, 1990). Rate ofloss then gradually decreases over thenext few weeks.

The losses in maximal voluntary forceresult only partially from the muscleatrophy. It is thought that reduced neuralinput is also in part responsible for the large reductions seen in maximalvoluntary force during periods of in-activity (Berg et al, 1997). Supporting

evidence comes from studies during spaceflight in which an astronaut’s peak legpower decreased by 54% after 21 days ofweightlessness (Antonutto et al, 1998).This was in comparison to a reduction inpeak power of 20% seen in studies ofsingle soleus fibres after 17 days of spaceflight (Widrick et al, 1999). This suggeststhat factors other than atrophy maycontribute to decline in peak power (Fittset al, 2001).

Increased Activity or TrainingAs stated earlier, change in skeletalmuscle activity results in change inexpression of myosin heavy chainisoforms. Theoretically, increased activityshould result in greater expression of slow myosin heavy chain and hence moretype 1 fibres, but the nature of the activityalso affects their expression. Whereasaerobic activity does seem to trigger theexpression of slow myosin heavy chain,weight-lifting training induces a greaterexpression of fast myosin heavy chain(Gea, 1997). It is believed that evenmoderate loads are capable of modifyingthe genetic expression, but the minimumthreshold required to induce thetransformation is not known.

The effect of increasing muscle activitymay vary according to the initial trainingstatus of the muscle concerned, ieatrophied, normal and hypertrophiedmuscle may all respond differently.Studies of increased muscle activity inhumans have focused on muscle responseto:

� High resistance with low numbers ofrepetitions (strength-type training)(Hakkinen et al, 1998; Kraemer et al,l996; Staron et al, 1994).

� Low resistance with high numbers ofrepetitions (endurance-type training)(Demirel et al, 1999; Fitts and Widrick,1996).

The four main principles of training any skeletal muscles (Fahey, 1998) areoverload, specificity, reversibility andindividuality.

Overload refers to the intensity of thetraining stimulus, and is accomplishedwhen more demand is placed on themuscle than is required for normal daily activity. ‘Normal’ requirements arethemselves poorly defined, and so it is not

Table 3: Key factors affecting degree ofskeletal muscle atrophy due to reducedactivity

Initial muscle fibre type composition (slow postural muscles, like soleus, atrophy at agreater rate than faster muscles).

Length of period of inactivity (there is a rapidrate of atrophy in the first few weeks ofinactivity, which then reduces).

Position during inactivity (most atrophy occurswhen the muscle is fixed in the shortenedposition).

Muscle situation (lower limb muscles atrophyfaster than upper limb muscles).


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surprising that the critical amount andnature of the required overload is also illdefined. As will be seen, differentoverload stimuli can be used to producedifferent muscle adaptations, but theprinciple of progressive overload is afundamental requirement for bothstrength and endurance training pro-grammes. This states that for strengthtraining a muscle must be worked againsta load that is greater than normal, andthat as the muscle gains strength, so theload must be increased to stimulatefurther strength gains. For endurancetraining this means that the trainingvolume (duration and frequency) orintensity should be progressivelyincreased. Continual reassessment istherefore essential to ensure that overloadis maintained during training

Specificity relates to the nature of theadaptations occurring as a result oftraining. High repetition or intensitycombined with low load training leads toadaptations which improve endurance,whereas low repetition or intensity andhigh load training leads to adaptationswhich improve strength. The principle ofspecificity dictates that although theseadaptations are not mutually exclusive,one or the other type can be promotedthrough specific training programmedesign. Specificity also refers to otherfactors in the training programme such asspeed of shortening and position at whichcontractions occur.

Reversibility is the transient nature ofmuscle adaptations to training. Theprinciple of reversibility states that atrained muscle that ceases training, or anormal muscle that becomes inactive, will both undergo biochemical andmorphological changes as a result.Strength or endurance gains will be lostunless a maintenance programme ofsufficient intensity is undertaken.

Individuality refers to the fact thatindividual variability will affect thetraining response to a given programme.This variability comes from heredity, aswell as variations in cellular growth rates,metabolism and neural and endocrineregulation (Wilmore and Costill, 1994).These factors will determine how quicklyand to what degree adaptations occur inresponse to training.

Two additional principles that affectskeletal muscle training are the force-length relationship (Norkin and Lev-angie, 1992) and the force-velocity relat-ionship (Epstein, 1994). The implicationsof the force-length relationship are thatmuscles will acquire maximal strengthgains at the length at which they aretrained. Thus for general peripheralskeletal muscle training it is recognisedthat training must be carried out atvarious joint angles to ensure strengthgains throughout the range of motion.

The force-velocity relationship meansthat speed of shortening will also affectthe force of contraction generated.Skeletal muscle training with high forceand low velocity contractions willspecifically increase maximal force andnot maximal shortening, whereas train-ing with low force and high velocitycontractions will specifically increasemaximal shortening velocity and notmaximal force. In simple terms, lifting aheavy weight slowly will increase strengthof contraction, whereas lifting a lighterweight quickly will increase speed ofcontraction.

Strength TrainingMuscle strength has been defined as theability of a muscle or group of muscles toproduce tension and a resulting force inone maximal effort, either dynamically or statically, in relation to the demandsupon it. Thus an increase in strength willenable the muscle to resist an increasedload. In normal subjects, muscle strengthcan easily be increased by training,provided that the training loads usedexceed those of normal daily activities(Komi and Hakkinen, 1991). The greaterthe training load, the greater will be theincrease in strength. On the other hand,if muscular activity levels are lower thannormal, then strength will decrease. In between these two lies the ‘forcemaintenance zone’ where daily tensionlevels are enough to maintain the forcecapacity of a muscle at the same level. Theresponse to training of any muscle willdepend on its initial status (ie normal,hypotrophic or hypertrophic). Thetraining zone can be defined as loadsranging from 60% to 100% of maximalvoluntary per formance for normalsubjects, and 80% to 100% for athletes(Komi and Hakkinen, 1991). Maximalvoluntary per formance refers to the


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maximum force exerted at a singlerepetition (known as the 1 RM). Theforce that can be exerted ten times, or 10 RM, corresponds to approximately75% of the 1 RM.

Neural Adaptations At one time it was believed that thestrength gains seen as a result of trainingwere simply as a result of musclehypertrophy. It is now clear that strengthgains are also due to other factors,particularly in the early stages of training.Enoka (1988) has argued that strengthgains can be achieved without structuralchanges in muscle, but not without neural adaptations.

Various studies have demonstrated thatthe measured integrated electromyo-graphic activity changes in parallel withincreases in muscle strength (Komi, 1986;Moritani and DeVries, 1979). Integratedelectromyographic activity represents themuscle’s level of neuronal activation.

Neural adaptations may include imp-roved co-ordination, increased inhibit-ion of antagonists and increased activ-ation of prime movers (Sale, 1986). Theimplication is that untrained muscles havean appreciable functional reserve that isnot readily available for use, despitepresumed maximal effort. This can bemobilised with appropriate training, and improve the co-ordination of motor unit activation (Milner-Brown et al,1975).

Moritani and de Vries (1979) found thatprogressive resistance training haddifferent results in different age groups.Neural adaptations were responsible foralmost all the strength gains seen in theirolder group (average age 70 years) duringan eight-week training programme. Intheir younger group (average age 22years) neural factors were dominant inthe first four weeks of training, but in thelast four weeks muscle hypertrophybecame the dominant feature. Thissuggests that muscle ability to hyper-trophy may decrease with increasing age.

Morphological Adaptations Generalisations about the effects ofstrength training are confounded by lackof agreement over the definition of terms(eg strength) and by use of non-specificforms of exercise. Some broadly acceptedeffects of strength training are as follows:

� Increased expression of MHC-2A anddecreased expression of MHC-2Xisoforms (Baldwin and Haddad, 2001).

� Increase in cross-sectional area of bothtype 1 and type 2 fibres, with type 2increases occurring at a faster rate(MacDougall et al, 1980).

� The increase in cross-sectional area oftype 2 fibres correlates with maximalisometric strength (Rose et al, 1982).

� Changes in metabolic capacity dooccur, but show no definitive pattern.

Although changes in muscle proteinsoccur after only a few sets of high resist-ance exercise (Scott et al, 2001), visiblemuscle hypertrophy is not evident forseveral weeks (Kraemer et al, 1996).

Stimulus The stimulus to produce musclehypertrophy is not yet clear. Hormonalinfluences, eg testosterone, are likely but levels of blood testosterone correlatepoorly with the degree of training-induced hypertrophy (Wilmore andCostill, 1994). Thyroid hormone is alsobelieved to have a role in regulatingmyosin heavy chain gene expression(Baldwin and Haddad, (2001).

Mechanical factors such as change in tension are also likely to contribute(Talmadge, 2000). MacDougall (1986)described the way body-builders visualisetheir training as breaking down muscleprotein which is subsequently rebuiltbetween training sessions.

This simplistic early model has beensupported by studies suggesting that somedamage does occur during strengthtraining (Vierck et al, 2000; Friden andLieber, 1992) and that during exercise,protein synthesis decreases while proteindegradation increases (Goodman, 1988).

It is possible that any damage isrepaired during rest periods, and that thecyclical damage and repair could lead tothe overshoot of protein synthesis seenduring the period after exercise(Goodman, 1988). This idea is supportedby findings that the greatest increases inmuscle size and strength are producedwhen two or three days of rest are allowedbetween training sessions for specificmuscles, and that more frequent trainingwill cause muscle size and strength todecline.

Hypertrophy is thus a delayed phen-


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omenon occurring late after the onset of training and requiring rest periodsbetween bouts of training. Hypertrophy of muscle fibres may depend not only onthe type of training used, but also theenhanced motor unit recruitment. As thestrength of a muscle increases, so does itscardiovascular response, thus increasingmuscle endurance. Although the detailedmechanism for fibre size enlargement isnot clear, a pre-requisite is that trainingloads are maximal or near maximal, andthat the total stimulus duration is longenough.

HyperplasiaThere is evidence from animal studiesthat hyperplasia (an increase in thenumber of muscle fibres) occurs andcontributes to muscle hypertrophy. Ameta-analysis by Kelley (1996) reviewedthe effects of mechanical overload onnumbers of skeletal muscle fibres inanimals. He concluded, from the 17studies meeting his inclusion criteria, thathyperplasia occurs in several animalspecies, particularly as a result of chronicstretch. These results have yet to bereplicated in humans.

Endurance Training Muscle endurance has two inter-pretations. It can be defined as the abilityof a muscle to contract repetitively or to sustain a single contraction over aprolonged period (Kisner and Colby,1990). Precise definitions of ‘prolonged’are not given. An increase in muscleendurance will enable a muscle toperform more repeated contractions orsustain a single contraction over anextended period of time.

Muscle endurance is increased byper forming exercises against a mildresistance for many repetitions. Mostprogrammes designed to increase musclestrength will result in an increase inmuscle endurance. Endurance training,also known as aerobic training, leads to anumber of changes in skeletal muscle.Increased tension provokes the repressionof fast type and activation of slow typegenes, implying a progressive trans-formation in type of fibres. This is not dueto fibres being substituted, but to changesin the expression of their myosin heavychain isoforms. The following changeshave been observed in response toendurance training:

� Change in expression of myosin heavychain isoforms ie MHC-2X to MHC-2A(O’Neill et al, 1999). Increasedexpression of MHC-1 (Andersen andAagaard, 2000).

� Increase in cross-sectional area oftype 1 fibres. No change is seen in theproportions of type 1 and type 2 fibres,but there is some evidence that type2X fibres may take on thecharacteristics of type 2A fibres (Ricoyet al, 1998; Pette and Staron, 1997).

� Increase in the number of capillariessurrounding each muscle fibre. Thisoccurs within the first few weeks oftraining and allows greater exchangeof gases, heat, nutrients, etc, betweenmuscle fibres and blood (Hermansenand Wachtlova, 1971).

� Increase in myoglobin content.Myoglobin is a compound similar tohaemoglobin to which oxygen bindson entering the muscle fibre. Type 1fibres have larger quantities ofmyoglobin than type 2 fibres.Myoglobin stores the oxygen and thenreleases it to the mitochondria duringthe transition of the muscle state fromresting to active (Terrados et al, 1990;Holloszy, 1976).

� Increase in size and number ofmitochondria (Tonkonogi et al, 2000).

� Increase in activity of oxidativeenzymes, eg succinate dehydrogenaseand citrate synthase. The role of thisincreased activity is not clearlyunderstood as there is only a weakrelationship between recorded activityand VO2 max (Melissa et al, 1997;Costill et al, 1979).

� Increased glycogen and fat storage inmuscle (Holloszy, 1976).

� Increased activity of enzymes involvedin beta-oxidation of fat (Holloszy, 1976).

� Increase in lactate threshold (ie workload at which lactatesignificantly accumulates in the blood)(Holloszy, 1976).

Angiotensin Converting Enzyme Gene and Muscle PerformanceAngiotensin is one of a number ofhormones that regulate the circulatorysystem. There are two types: 1 acts as avasodilator and 2 as a vasoconstrictor. Theangiotensin converting enzyme changes


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type 1 into type 2 angiotensin. In add-ition, local renin-angiotensin systems mayinfluence tissue growth.

Angiotensin converting enzyme inhuman skeletal muscle can be encoded byeither of two variants of the gene. Thelonger variant (the insertion allele -- I) is associated with lower enzyme activity,and the shorter variant (the deletionallele – D) is associated with higherenzyme activity. They are equallycommon, meaning that the Britishpopulation can be divided into 25% whoare II (with low angiotensin convertingenzyme activity) 50% who are ID (withintermediate activity) and 25% who areDD (with high activity). There is evidencesuggesting that muscle growth might bepositively associated with the deletionallele.

Folland et al (2000) studied normalsubjects over nine weeks of specificquadriceps strength training. They founda consistent genotype and traininginteraction whereby those with thedeletion allele had significantly greatermuscle hypertrophy and strength gains.On the other hand, some studies havesuggested that endurance performance isassociated with the insertion allele.Among British Olympic-standard runners,a linear trend of increasing insertionallele frequency with distance run wasfound (Myerson et al, 1999). This trendhas also been seen in high altitudemountaineers, so that of 15 climbers whohad ascended beyond 8,000 metreswithout oxygen, none was DD genotype(Montgomery and Brull, 2000). Gayagayet al (1998) found a higher frequency ofthe insertion allele in Australian rowersthan sedentary controls.

There has also been some preliminaryexperimental work examining the rel-ationship between angiotensin convertingenzyme genotype and response to muscleendurance training. Montgomery et al(1998) found that repetitive elbow flexionimproved in a genotype-dependentfashion after ten weeks of training. It isnot known how the II angiotensinconverting enzyme genotype mightimprove the mechanical efficiency of themuscle, but it may be related to anincrease in type 1 fibres (Williams et al,2000). Angiotensin converting enzymeinhibitor drugs are a recognised therapyfor cardiac dysfunction. It is possible that

part of their effect is to improve themetabolic performance of skeletal andcardiac muscle (Montgomery and Brull,2000). If there is a link between lowangiotensin converting enzyme activityand muscle efficiency, then in future itmay be possible to manipulate situationswhere whole body oxygen and substratedelivery are compromised, such asunstable angina, adult respiratory distresssyndrome and pancreatitis (Myerson et al,1999).

Not all studies have supported thehypothesis, however, as some have foundno association between the angiotensinconverting enzyme genotype andendurance performance (Rankinen et al,2000; Taylor et al, 1999). The study byRankinen et al compared 192 enduranceathletes with controls and found nosignificant differences. Taylor et alcompared 120 athletes from aerobicsports (eg hockey, cycling, skiing) with acommunity control group randomlychosen via electoral roll. These numbersmay not have been enough to detectangiotensin converting enzyme genotypeinfluence.

However, the studies presenting positivefindings have generally involved smallernumbers of subjects (25 to 91) than thenegative studies. There is also thepossibility of publication bias towardspositive findings, so that more positivestudies are available. Therefore, althoughthe underlying theory is interesting, it isprobably too early to draw any firmconclusions about the angiotensinconverting enzyme genotype and humanperformance.

ConclusionAlthough muscle response to alteredpatterns of activity has been extensivelystudied, there are still many areas ofuncertainty. Physiotherapists are wellaware that periods of reduced activityimpair neuromuscular performance.However, there are still few guidelines as to the optimal load, frequency orrepetitions needed to prevent thisimpairment, maintain normal functionand/or improve performance. One of the reasons for this is the individuality of responses to exercise. The gene-environment interaction is complex, butit is possible that genotype may determinethis phenotypic response.


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Key Messages

� Skeletal muscle alters in response toenvironmental changes.

� Periods of increased or reducedactivity have significant effects on allskeletal muscles.

� There is no consensus as to theoptimal mode or strategy forpreventing or promoting theseeffects.

� The angiotensin converting enzymegenotype may affect individualresponse to training.

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