Download Whole body protein synthesis is an average of the synthesis rates

Sarcoplasmic Hypertrophy and Rep Range
By Dan Moore
One of the issues I still see when reading training articles is how the rep range
dictates whether any hypertrophic response predominantly influences changes in size
of the contractile components of muscle cells or the sarcoplasmic volume. The intent
of this article is not to dispute that sarcoplasmic hypertrophy exists but to clarify if
the rep range used will dictate which protein fraction will increase and whether or not
the rep range specifically induces different changes to the nuclear domain of muscle
fibers.
There may very well be other factors such as metabolite accumulation and osmolality
shifts within the cell that would give temporary changes to the muscle cell volume
and size but since these are mostly temporary I did not feel they should be included
in this article.
What is the Sarcoplasm?
Within the sarcoplasm there are soluble (or aqueous) components (making up 80
percent of it); composed of ions and soluble macromolecules like enzymes,
carbohydrates, different salts and proteins, as well as a great proportion of RNA. This
watery component can be more or less gel-like or liquid depending on the condition
and the activity phases of the cell. In general, margin regions of the cell are gel-like
and the cell's interior is liquid.
The insoluble constituents of the sarcoplasm are organelles (such as the
mitochondria, the chloroplast, lysosomes, peroxysomes, ribosomes), several
vacuoles, cytoskeletons as well as complex membrane structures (e.g. sarcoplasmic
reticulum).
The muscle protein fraction that makes up the cytoplasm (sarcoplasm in a muscle
cell) is made up of mostly enzymes participating in cell metabolism, such as the
anaerobic energy conversion from glycogen to ATP, intracellular transport, and
several other enzyme functions. This fraction adds up to about 25 or 30% of the total
muscle protein versus the larger and more talked about structural protein (myofibril
protein) makes up about 40%.
Skeletal muscle protein
When speaking of protein synthesis one of the things that first must be identified is
which fraction of protein we are talking about.
Whole body protein synthesis is an average of the synthesis rates of various proteins
in different tissues of the body, skin, muscle, organs, and plasma.
Mixed muscle protein is an average of the synthesis rates of total muscle proteins
and includes mitochondrial, sarcoplasmic, structural components and connective
tissue proteins.
Myofibrillar protein is comprised of individual proteins such as myosin, actin, titin,
tropomyosin, troponin, protein C, and some components of mitochondrial proteins.
Sarcoplasmic proteins are mostly enzymes participating in cell metabolism. However,
if the organelles within the muscle cells are broken, this protein fraction may also
contain the metabolic enzymes localized inside the sarcoplasmic reticulum,
mitochondria and lysosomes.
Fractional Protein Synthesis
It has now been known for some time that chronic elevation in protein synthesis
above that of breakdown is of prime importance in skeletal muscle hypertrophy
(1,2). It is this basis of understanding that we start this article off by looking into
how feeding and exercise impacts fractional protein turnover.
Years ago David Millward and Peter Bates identified that protein synthesis had a
direct relationship to both feeding and fasting (3). They also noted that during tissue
growth (from feeding) the maintenance of a constant composition necessitates the
same absolute increase in synthesis for all proteins, both contractile (myofibril) and
soluble (sarcoplasmic). This would mean that the increase in the synthesis rate for
each protein will be an increasing proportion of the overall rate for the slowerturning-over proteins or in more simpler terms, the increase of both fractions are
held within a ratio.
Resistance training has shown very strong shifts in protein turnover (4,5) and most
of the studies have used mixed muscle protein turnover as the gauge of
effectiveness. Unfortunately this method does not show how resistance or dynamic
exercise training differently affects each fraction.
In a study looking at age affects of Protein Synthesis (6) it was noted that by the
end of 2 weeks of weight-lifting exercise, MHC and mixed protein synthesis rates
increased in both younger and older participants. The actin protein synthesis rate
was increased after exercise in only the younger group. The magnitude of the
exercise-induced increase in MHC and mixed protein synthesis rates was similar in
the younger and older groups. In the younger group, the MHC and Actin (contractile)
protein synthesis rate increased 83% and 78% respectively while the mixed muscle
protein synthesis rate increased (102%). This study points to the identification that,
as with feeding, all proteins are up regulated with resistance exercise. Now the
interesting point was that the exercise protocol used seven weight-lifting exercises
(Nautilus equipment) that included the chest press, inclined chest press, latissimus
pull-down (wide and narrow grip), leg press, knee extension, knee flexion, and two
free weight-lifting exercises that included seated overhead press and overhead
triceps extension. Each participant completed ten weight-lifting exercise sessions: 2–
3 sets/day of the nine exercises listed above, 8–12 repetitions/set, 60–90% of
maximum voluntary muscle strength. This was a pretty broad range of intensity and
easily points out that the rep range itself isn’t the determining factor.
To further illustrate that the intensity or rep range utilized does not change this ratio
all too dramatically we can look at more recent work looking into the synthetic rates
of fractional proteins with dynamic or resistance type exercise.
Atherton et al. (7) used electrical stimulation with high frequency (HFS; 6x10
repetitions of 3 s-bursts at 100 Hz to mimic resistance training) to identify signalling
present during increased protein synthesis. What he noted, significant to this article
and discussion, was that HFS significantly increased myofibrillar and sarcoplasmic
protein synthesis 3 h after stimulation 5.3 and 2.7 fold, respectively.
Interestingly Bowtell (8) found that when the same total amount of ATP is turned
over, exercise at 60, 75 and 90% of the one-repetition-maximum force results in
exactly the same stimulation of muscle protein synthesis, suggesting that once all
muscle fibers are recruited increases in tension above 65% cause no further
stimulation in muscle protein synthesis. Even though I am not aware if the specific
fractions were measured in the Bowtell study it would stand to reason that in light of
the previous both fractions would be up regulated.
In another study, Louis (9) subjects carried out 20 series of 10 repetitions (with a
rest of 80 s after each series) on an isokinetic dynometer to evaluate if Creatine has
an impact on anabolic signalling and protein synthesis. Again, in the realm of this
article, what was found interesting was that this exercise increased the synthetic
rates of myofibrillar and sarcoplasmic proteins by 2- 3 fold.
Looking at dynamic exercise (one legged kicking), Miller (10) saw that the rates of
protein synthesis in the exercised leg increased substantially by 6 h and peaked
within 24 h in both myofibrillar and sarcoplasmic fractions, i.e. increases of 2.8 and
2-fold, respectively. The rates of myofibrillar and sarcoplasmic protein synthesis in
the exercised muscle had fallen slightly by 48 h but were still significantly above the
rates in the rested leg. By 72 h, the rates of both fractions had decreased.
Our last look at fractional elevations will look at whether or not there is a fiber type
dependency. In many animals the rate of protein synthesis is higher in slow-twitch,
oxidative than fast-twitch, glycolytic muscles. To find if this held true for muscles in
the human body a recent study (11) recruited nine healthy, young men and with a
constant infusion looked at synthetic rates in the soleus, vastus lateralis and tricep.
Type-1 fibers contributed 83 +/- 4% (mean +/-s.e.m.) of total fibers in soleus, 59
+/- 3% in vastus lateralis and 22 +/- 2% in triceps. The basal myofibrillar and
sarcoplasmic protein fractional synthetic rates (FSR, % h(-1)) were 0.034 +/- 0.001
and 0.064 +/- 0.001 (soleus), 0.031 +/- 0.001 and 0.060 +/- 0.001 (vastus), and
0.027 +/- 0.001 and 0.055 +/- 0.001 (triceps). During amino acid infusion,
myofibrillar protein FSR increased to 3-fold, and sarcoplasmic to 2-fold above basal
values (P < 0.001), again showing that even within differing types of muscle tissue
the ratio remains.
What can be seen when reviewing these and many other papers on the subject is the
response to resistance training of fractional elevation remains in line with the results
of feeding, both are elevated but the slower turnover proteins (myofibrillar) generally
show a larger magnitude in increase. Since these studies show that this holds true
with resistance training, dynamic exercise and HFES, all utilizing differing intensities
and work output, it seems unlikely that the rep range is the sole cause of any
increase in sarcoplasmic fraction up-regulation.
Nuclear Domains
It is well established that satellite cell contribution is a very important factor in
muscle hypertrophy (12,13). As a cell grows and increases it’s cytoplasmic volume
the nucleus must maintain mRNA production for the entire area of increased size of
cytoplasm (14). Since muscle cells are multi-nucleic, each nucleus controls mRNA
over a finite area or its domain (14,15), hence the term nuclear domain.
Skeletal muscle hypertrophy has shown to induce increases in myonuclei and or
increases in domain size (16). Resistance training has reported a very broad range of
increases in fiber hypertrophy (17). In several hypertrophy studies it appears that
there is a limit that needs to be reached before domain size increases necessitates
increased nuclei donation. Studies that have shown significant increase in
hypertrophy, above 26%, also showed large additions of myonuclei in animals (1820) and in humans (21).
Work in humans is rather limited but what can be seen in this smaller body of work
is very interesting. Acutely, resistance training and resistance type training do not
exert the same magnitude of response in humans as what is seen in smaller animals.
A recent study (22) examining the acute effect of training showed less significant
changes in donated nuclei and in fact after an acute bout of (a) fifty one legged ‘drop
down’ jumps were performed from a stable platform of 45 cm, (b) eight sets of ten
maximal eccentric knee extensions at –30 degree/s using an isokinetic dynamometer
and (c) eight sets of ten maximal eccentric knee extensions at –180 degree/s using
an isokinetic dynamometer, satellite cell proliferation did occur but there was no
increased satellite cell donation. Apparently a single bout in humans is not enough to
induce the same changes seen in smaller animals.
Kadi looked at chronic application in a very interesting and telling look at training
and detraining. (23). In this study he subjected 15 subjects to 3 months of
progressive resistance training using a 6-12 RM. The various exercises were
conducted in 4–5 sets, in the first weeks (training sessions 0–5) exercises involved
10–12 RM loads, followed by 10 RM loads in early weeks (training sessions 6–15),
heavier loads of 6–10 RM in the later weeks (training sessions 16–30), and very
heavy loads of 6–8 RM in the final weeks (training sessions 31–38). The subjects
then detrained for 3 months. Satellite cell activity increased significantly over the
entire training period. Reaching significance at around 30 and again at the 90-day
marks. Hypertrophy of fiber increased at 30 days and 90 days, 6.7% and 17%
respectively. Interestingly though was the observation that the area controlled by
each nuclei was virtually unchanged over the entire training period. This clearly
illustrates that the rep range was not the primary inducer of hypertrophy or domain
volume changes since the fiber size and satellite cell count increased no matter the
rep range. It also clearly indicates that the duration of chronic training is a key
element in both hypertrophy and satellite cell activity.
An earlier study by the same researcher (24) saw a concomitant increase in satellite
cell count and an increase in myonuclei donation over a 10-week training protocol in
female athletes. The muscle examined in this study was the trapezius so it could be
that the increase could be muscle specific, as it’s been shown that the trapezius has
a higher androgen receptor content (25). This may have also been another reason
why the previously cited work by Kadi showed such a difference as the biopsies were
taken from the vastus lateralis.
In summary it is very common to see studies reflecting both increased protein
synthesis and hypertrophy with a myriad of rep ranges and resistance training
protocols. The extent of hypertrophy may be a direct reflection in increased
translational efficiency or an increase in pre-translational abundance of mRNA. The
differences may be owing to the training status of the individual and not necessarily
the rep range used in the resistance training routine. Although it appears that the
rep range will have an impact on metabolic shifts in isoform content this does not
change the sarcoplasmic vs. contractile protein synthesis ratio but merely dictates
which fiber type will experience the greater amount of hypertrophy.
As stated in Rennie’s 2004 review (26), it may take 20 weeks of resistance training
to increase hypertrophy by 20%. This coincides very well with the research
presented in this article, as it appears that the change in fiber size has a direct
correlation to when satellite cells donate their nuclei for continued domain regulation.
Therefore moderate increases in nuclear domain are very possible without the aided
donation of nuclei from satellite cells and this does not appear to be rep range
dependant. A statement can also be made that the results seen in small animals and
humans may be very different. This may be owing to the extent of damage that is
seen and how hypertrophy and necrotic damage stimulate the satellite pool
differently but that is beyond the scope of this article.
Dan Moore
Hypertrophy-Research.com
(1)Changes in rates of protein synthesis breakdown during hypertrophy of the anterior and posterior
latissimus dorsi muscles. Biochem. J. 176:407–17
(2)Protein turnover during skeletal muscle hypertrophy.Fed. Proc. 39:42–47
(3)Synthesis rates of myofibrillar and sarcoplasmic protein fractions in different muscles and the changes
observed during postnatal development and in response to feeding and starvation Biochem. J. (1983)
214,587-592
(4)Increased rates of muscle protein turnover and amino acid transport after resistance exercise in
humans. Am J Physiol Endocrinol Metab 268: E514–E520, 1995.
(5)Changes in human muscle protein synthesis following resistance exercise. J Appl Physiol 73: 1383–
1388,1992.
(6)Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78–84 and 23–
32 yr olds Am J Physiol Endocrinol Metab 278: E620–E626, 2000.
(7) Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive
responses to endurance or resistance training-like electrical muscle stimulation. FASEB J. 2005
May;19(7):786-8. Epub 2005 Feb 16.
(8) Stimulation of human quadriceps protein synthesis after strenuous exercise: no effects of varying
intensity between 60 and 90% of one repetition maximum (1RM). J Physiol 547.P, P16.
(9) No effect of creatine supplementation on human myofibrillar and sarcoplasmic protein synthesis after
resistance exercise. Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E1089-94.
(10)Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle
after exercise.J Physiol. 2005 Sep 15;567(Pt 3):1021-33.
(11)Protein synthesis rates in human muscles: neither anatomical location nor fibre-type composition are
major determinants. J Physiol. 2005 Feb 15;563(Pt 1):203-11. Epub 2004 Dec 20.
(12)Gamma irradiation prevents compensatory hypertrophy of overloaded mouse extensor digitorum
longus muscle. J. Appl. Physiol. 73:2538–43
(13)Cellular molecular responses to increased skeletal muscle loading after irradiation. Am. J. Physiol.
Cell Physiol. 283:C1182–95
(14)The control of cell mass and replication. The DNA unit-a personal 20 year study. Early Hum Dev 12,
211-239.
(15) Nuclear Domains in Muscle Cells. Cell 59, 771-772
(16)Regulation of Skeletal muscle fiber size, shape and function. J Biochem (Suppl. 1), 123-133
(17) Exercise, protein metabolism, and muscle growth. Int J Sport Nutr Exerc Metab. 2001
Mar;11(1):109-32. Review.
(18)Morphometric analyses on the muscles of exercise trained and untrained dogs. Am J Anat. 1983
Mar;166(3):359-68.
(19)Plasticity of myonuclear number in hypertrophied and atrophied mammalian skeletal muscle fibers. J
Appl Physiol. 1995 May;78(5):1969-76.
(20)Modulation of myonuclear number in functionally overloaded and exercised rat plantaris fibers.J Appl
Physiol. 1999 Aug;87(2):634-42.
(21)Is Hypertrophy limited in elderly muscle fibers? A comparison in elderly and young strength-trained
men. Basic Appl Myol 1998; 8, 419-427
(22)Changes in satellite cells in human skeletal muscle after a single bout of high intensity exercise. J
Physiol. 2004 Jul 1;558(Pt 1):333-40.
(23)The effects of heavy resistance training and detraining on satellite cells in human skeletal muscles. J
Physiol. 2004 Aug 1;558(Pt 3):1005-12.
(24)Concomitant increases in myonuclear and satellite cell content in female trapezius muscle following
strength training. Histochem Cell Biol 2000; 113, 99-103.
(25)The expression of androgen receptors in human neck and limb muscles: effects of training and selfadministration of androgenic-anabolic steroids. Histochem Cell Biol. 2000 Jan;113(1):25-9.
(26)Control of the Size of the Human Muscle Mass Annu. Rev. Physiol. 2004. 66:799–828