Repertorio inicial

Two types of muscle contractions that have been used to investigate the characteristics

of muscle force development are twitch and tetanic contractions. Twitch contractions

are the response to a single action potential, whereas tetanic contractions occur when

impulses are delivered so quickly that there is inadequate time for calcium to be pumped

back into the SR and [Ca2+]i remains elevated. Thus, maximum muscle force output

occurs in a tetanic contraction.

The force of tetanic contractions can be influenced by numerous factors, which include

intracellular calcium concentration, cross-bridge phosphorlyation, elasticity and

biomechanics, and as mentioned previously, muscle size (cross-sectional area).

Sarcomere length is also an important factor in determining maximal tetanic contraction

(maximum muscle strength). It is well acknowledged that force developed by a muscle

uring a maximum isometric tetanic contraction (where length of muscle remains the

me) is a direct function of the magnitude of overlap between actin and myosin

laments (i.e. its starting sarcomere length; Schoenberg and Podolsky, 1972;

98). In short, maxi be achieved during the plateau

hase the length-tension curve (figure 1.4) when a muscle fibre is at its optimal

ngth hence has its greatest myofilament overlap (i.e. maximum number of cross-

ridge rmation). The descending limb of the length-tension curve indicates stretching

f the sarcomeres. Active stretching of the sarcomeres during the descending limb of the

ngth-tension curve (eccentric con pt to this thes s it is

plicated in the initial event that leads to skeletal uscle injury (Section 2.1.1.1.1). d

sa

fi

Schoenberg, 19 mal force output can

p of

le ,

b fo

o

le traction) is an important conce is a

.1.3.3 Muscle Metabolism

s muscle contraction occurs, ATP provides the energy for contractile events (cross-

ridge movement and attachment). Since ATP is the only energy source that can be

sed directly for contractile activities, it must be generated continuously if contraction is

to continue. The conventional view of the energy transfer leading to muscle contraction

is depicted in figure 1.5, which shows that ATP is formed in the mitochondria and

diffuses to myofibrils. ADP, formed by hydrolysis of ATP by the globular heads of the

olecules, diffuses back to the mitochondria, stimulating respiratory activity in Normal Working

Range ress

Figure 1.4. Length – Tension curve. (kg/cm2) St 1 A b u myosin m

the process called respiratory control (Bessman and Geiger, 1981).

Sarcomere length (µm)

0 1 2

3

4

1

2

3

4

Length (fraction of optimum)

L

o

0 1 2

3

4

3

4

Active Passive Total

2

1

ATP → ADP + Pi

Figure 1.5. The phosphocreatine energy shuttle (taken from Saks et al., 2000).

While ATP resynthesis can occur locally on myofibrils and biomembranes due to

activity of CK and glycolytic enzymes as shown above in figure 1.5, it is suggested that

their exists site-specific regeneration of ATP, which creates a local pool of ATP in close

vicinity of sites of ATP utilization (Korge et al., 1993). An important concept to this

thesis is the energy regulation of the SR Ca -ATPase pump. The SR Ca -ATPase

pump is the most energy-demanding pump in the muscle (Rossi et al., 1990). Calcium

uptake requires the direct coupling of CK to the SR Ca -ATPase, in which CK

catalyses the reversible transphosphorylation of the high energy N-phosphorly group of

phosphocreatine (PCr) to ADP, regenerating ATP (Equation 1; Walliman et al., 1992).

CK

MgADP + PCr + H MgATP + Cr Equation 1.

In skeletal muscle, small amounts of CK are bound in an isoenzyme-specific fashion to

subcellular structures such as inner mitochondrial membrane (Mi-CK) (Saks et al.,

1978), and the M band in myofibrils (Walliman et al., 1977). Interestingly, Rossi et al.

(1990) demonstrated the existence of a muscle-type MM creatine kinase isoform that is

specifically bound to the SR. It is suggested that MM-CK bound to the SR, which ATPase

(muscle contraction)

2+ 2+

2+

preferentially uses the creatine kinase-creatine phosphate (CK-PCr) system, may be

physiologically important in vivo for regeneration of ATP directly in the vicinity of the

SR Ca2+ pump, thus maintaining high ATP/ADP ratios (Rossi et al., 1990). It is

hypothesized that while high [ADP] levels in close proximity to the SR Ca2+ pump may

diminish its efficiency, high [ATP] to [ADP] levels could be essential in the

thermodynamic efficiency of ATP hydrolysis, and therefore improved calcium handling

ability of the muscle (Rossi et al., 1990).

Indeed, Korge and Campbell (1994) demonstrated that in the presence of creatine

phosphate, membrane-bound CK regulated ATP regeneration close to the SR Ca2+

ump by monitoring local increases in [ADP], and thus enhancing Ca2+ pump function.

s were obtained from rabbit fast-twitch skeletal muscles; Ca2+

uscle

rchitecture (structure) as mentioned previously, but fibre type, or fibre phenotype

redisposition. It has been well established (Close, 1972), that human skeletal muscle is p

Isolated SR vesicle

reuptake and efflux, and ATPase activity, thus Ca2+ handling ability of the muscle, was

measured by monitoring changes in extravesicular [Ca2+] with a Ca2+-sensitive

minielectrode. The efficiency of SR Ca2+ pump function was determined by the amount

of Ca2+ transported per ATP hydrolysed, and thus was expressed as a coupling ratio. A

coupling ratio greater than 1 indicated high efficiency for Ca2+ transport, while a

coupling ratio less than 1 indicated low efficiency. It was hypothesized that local ATP

regeneration by the membrane bound CK-CP system is one mechanism by which the

cell can significantly improve SR Ca2+ pump function, especially when the pump is

working at low efficiency, such as those seen during eccentric-induced damage.

In document Hildo Ariel Aguirre Daza: 28 años de carrera, formación y difusión del Arpa Llanera en la ciudad de Bogotá (página 76-79)