of the different muscle fiber phenotypes
plastic nature of the muscle fiber phenotype has been proved to be
accounted by the physiological control exerted by the variations in
motor neuron activity (26, 27, 37). The main consequence of the
neural stimulation is the increase of intracellular Ca2+
concentration but the mechanism by which this can be the link between
motoneurons activity and gene expression is still a debated issue.
However some of the gene transcription inducing promoters involved
specifically in expression of the two main type I and II fibers have
been suggested. Therefore a calcineurin-dependent transcriptional
pathway was found to control the expression of gene in slow twitch
fibers (5). The proposed mechanism consists in the direct control of
calcineurin on the phosphorylation state of nuclear factor of
activated protein (NFAT) and its translocation to the nucleus which
further causes the activation of the target slow-type muscle proteins
in cooperation with myogenic enhancing factor (MEF2) which responds
to multiple calcium-regulated signals (39) and others regulatory
proteins. Signaling pathway involving Ras and mitogen-activated
protein kinase (MAPK) has been also found to influence the generation
of slow fibers (24). Calcium-dependent calmodulin kinase activity is
also regulated by a low firing rate of the motor units (39).
Peroxisome-proliferator-activated receptor-gamma co-activator-1 alpha
(PGC-1α) activates transcription in cooperation with MEF2
and serves as a target for calcineurin signaling, which as mentioned
before is implicated in slow fiber gene expression (21).
shift in the predominant metabolic nature of the effort from aerobic
to anaerobic production of the energy is accompanied by a
corresponding response in the transcriptional control. In the study
by Grifon et al (2004), supplying the predominant slow twitch fibers
containing muscle soleus, with Six 1 and its cofactor Eya 1 caused
the proliferation of endogenous glycolytic enzymes and fast twitch
sarcomeric proteins concomitantly with down regulation of slow
oxidative transcription controlling factors. Another important
regulator in the type II fiber gene expression has been found to be
the hypoxia inducible factor-1α (HIF-1α). Its
found to correspond with essential hypoxic responses in maintaining a
constant ATP level in the cells (23). Therefore the higher
recruitment of type II fibers in performing maximal and supramaximal
exercise intensities can not be only accidentally associated with the
more pronounced hypoxia caused by such efforts.
can be concluded that the main transitional factor affecting
expression of the gene in muscle contractile proteins synthesis is
the dynamic of intracellular Ca2+
concentration. As cross-bridge cycle occurs only following the
reaction of calcium ions with troponin in exposing the myosin binding
sites of actin filament it results that the pattern of calcium
release in response to neural excitation must be mediated by a
different activity in Ca2+
pumps. Therefore ATP-dependent
pump SERCA, have been found to exist in three isoforms (22). From
these SERCA 1 has been found to be more expressed in type II whereas
SERCA 2 in type I muscle fibers.
summary, it can be stated that the different pattern in muscle
contraction caused by motoneurons activity triggers corresponding
transcriptional control which targets not only the expression of MHC
isoforms, but also glycolytic and/or oxidative enzymatic apparatus as
well as SERCA isoforms.
assessment of the muscle fiber phenotype
consists in evidencing the findings about molecular structure and
functioning of the muscle fibers using assessment of the skeletal
muscles behavior during exercise by different methods and procedures
which are less invasive and provide faster results.
most common approach in identifying the predominant type of muscle
fiber bundles recruited during contraction is investigation of muscle
contraction intensity and velocity and the corresponding energy turn
over. Muscle energy turnover can be addressed either by metabolic or
calorimetrically approach (38). Metabolic approach assumes summing
the muscle aerobic and anaerobic energy turnover while the
calorimetric way consists in measuring the muscle heat production and
power output. By in
vitro studies based
on the energetic cost of short tetani (6), the content of ATP and CP
that was found to be proportional with contraction velocity (7) and
the heat release during contraction (2) it has been established that
in type II contraction velocity is 3-5 times higher then type I
accordance to the findings of these thorough investigations it has
been noted that the physiological adjustments occurring in the human
body during exercising at different exercise intensities were
In this regard the oxygen uptake kinetic has been found to present a
third slow component during higher exercise intensities indicating
higher oxygen consumption due to a higher recruitment of fast twitch
fibers (19, 28). This can be due to the lover mitochondrial content
and in general the reduced aerobic enzymatic equipment which causes
them to have lower efficiency in rephosphorylation of the nucleotides
based on oxygen use (16, 18). Moreover type II fibers have been found
to express the alpha glycerolphosphate shuttle involved in NADH
(nicotine adenine dinucleotide-dependent H+)
transport to higher degree than type I (31) which also explains their
lower efficiency in obtaining ATP within mitochondrial respiratory
these, the expression of uncoupling protein 3 (UCP3) was found to
correlate with the fraction of FT fibers in the human skeletal muscle
(14). It has been suggested that due to this protein, the leakage of
the protons across the mitochondrial membrane decreases P/O ratio
during exercise. Thus it can be suggested that the shift in the
recruitment pattern towards more FT fibers contracting during
exercise could increase the metabolic energy cost and thus decreases
the mechanical efficiency.
of the glycogen stores depletion during exercise revealed that the
higher exercise intensities were well correlated with the higher
consumption of the glycogen predominantly from type II fibers (9,
of ATP by the immediate phosphagen system namely CP (creatine
phosphate) dephosphorylation has been found to be significant higher
in type II fibers within intense exercises (30, 33). These are
explainable because CP as well as glycogen levels have been found to
be higher in type II fibers. Lactate release has been found to
increase in parallel with exercise intensity. An interesting finding
is that two of the major monocarboxylate transporters (MCTs) residing
in the muscle membrane cell and that are involved in lactate
transport have different properties in terms of their activity rate.
The MCT4 isoform which was predominantly found in fast twitch
glycolytic fibers has a relatively high dissociation constant (binds
easily but releases hardly the lactate molecule) Km
of 20-35 mM whereas MCT1 isoform more expressed in slow twitch
oxidative fibers has Km
of 3-5 mM (11, 20). This also shows the ability but also the
predisposition of type II fibers to produce and use the energy
anaerobicaly and this as it has been mentioned above supports the
higher velocity of skeletal muscle contraction.
4. Recruitment of the three main fiber types expressed depending on
firing rate and contraction intensity: type I (open squares), type
IIb (filled squares) and type IIb (filled triangles); based
on data from Hannerz 1974.
using muscle biopsy technique it is possible to asses the changes in
percentage expression of fiber types within a muscle as well as cross
sectional area and capillarization that have been influenced by the
specificity of designed protocol.
together indicate the existence of recruitment pattern according to
which low threshold type I fibers are recruited at low intensity and
high threshold type II fibers are recruited as exercise intensity
increases (13, 17) (Fig 4)
becomes interesting to make a parallel between laboratory work
findings and eyes free observations in terms of the correspondence
between velocity or/and intensity of contractions and the level of
oxygen consumption or heart rate ,when measuring of oxygen
consumption is not possible, being known that there is a close
relationship between heart rate and oxygen uptake (8). Surely,
completion of these with measurements of blood and muscle metabolites
comes and improves the accuracy in measuring the involvement degree
in terms of recruitment and activation level of the three main
skeletal muscle fibers.
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