Itt írjon a(z) cAMP_Muscle-ról/ről The Role of cAMP in Skeletal Muscle Cell Adaptation

Helena Pope Melanie Lean Josefin Jansson

INTRODUCTION

Cyclic adenosine monophosphate (cAMP) (see Figure 1 for structure) is a secondary messenger molecule, which helps to regulate numerous cell functions by way of signal transduction (Sjaastad et al, 2010). G protein (guanylate nucleotide binding protein) activates the enzyme adenlyl cyclase, which stimulates the formation of cAMP from ATP (adenosine triphosphate). cAMP subsequently binds to and activates protein kinase A, which is a key enzyme in the pathway of signal transduction (see Figure 2) (Sjaastad et al, 2010). Fluctuations in intracellular concentration of cAMP result in changes in cAMP dependent protein kinase activity (Korenman and Krall, 1977). The role of cAMP is extensive, much of which lies beyond the remit of discussion here (Rybalkin, et al, 2003). The review will instead focus on the role of cAMP in skeletal muscle adaptation.

Figure 1, Structure of cAMP (Adapted from Sjaastad et al, 2010

Figure 2, G protein pathway Adapted from Sjaastad et al, 2010

CHARACTERISTICS OF SKELETAL MUSCLE

Skeletal muscle is composed of large multinucleated cells and heterogeneous muscle fibres, which differ in their physiological and metabolic capacity (Rasmussen et al, 1987; Bassel-Duby and Olson, 2006). A direct correlation can be found between muscle strength and contractile ability, a key component of which is cAMP and its role in adaptation of skeletal muscle to exercise training (Rasmussen et al, 1987; Jorgensen et al, 2006). Skeletal muscle, in contrast to smooth muscle, exhibits repetitive contractile responses to recurring neural stimulation. Smooth muscle displays biphasic or monotonic contraction, the difference being the type of action potential created (Rasmussen et al, 1987).

cAMP EFFECTS ON MUSCLE MASS

Skeletal muscle is made up of units known as fibres (Nunamaker et al, 1985) (as seen in Figure 3). Fibres are classified by means of their expression of MHC (myosin heavy chain) isoforms, which are proteins with special contractile properties, and the way in which they generate energy (Rockl et al, 2007). Muscle myofibrils are able to physiologically respond to environmental demands by transforming and remodeling (Bassel-Duby and Olson, 2006). There are multiple signaling pathways involved, many of which interact with one another to reprogram gene expression in order to meet the demands of muscle performance.

Figure 3, INSERT HERE: DIAGRAM OF THE MUSCLE FIBRE AND ITS COMPONENTS

A key mechanism in muscle hypertrophy is the cAMP cascade (Bassel-Duby and Olson, 2006). Hypertrophy can be characterised by enlargement of cell size due to synthesis of cytoplasmic components in response to training (Glass, 2003: Sjaastad et al, 2010). Depending on the type of training- strength training or anaerobic training, the muscle responds accordingly by either increased sarcoplasmic volume, or increased contractile components (Helander, 1961). In contrast, atrophy can be recognised by a reduction in cell size (organelles, cytoplasm and proteins) as experienced during periods of muscle disuse/denervation (box rest/ equine non weight bearing lameness) and or disease (Glass, 2003; Bassel-Duby and Olson, 2006; Sandri, 2008).

MUSCLE FIBRE TRANSITION

Type I fibres exhibit slow twitch characteristics, meaning that they are able to cope with static or sustained forms of work load such as endurance running (Nunamaker et al, 1985). The source of energy in the form of ATP is mainly provided by means of oxidative (aerobic) pathways (Rockl et al, 2007). These fibres are often referred to as red muscle fibres.

Type II fibres are able to work faster but are quickly prone to fatigue, i.e. they are fast twitching and can also be referred to as white muscle fibre (Nunamaker et al, 1985). There are three subgroups assigned: IIa, IIx and IIb. The IIx and IIb fibres generate ATP mostly by means of the glycolytic (anaerobic) pathway. Type IIa, just like the slow twitching type I, works mainly aerobically (Rockl et al, 2007). Out of the three subgroups type IIb is considered to be the fastest muscle fibre, followed by IIx, IIa and finally type I (Pette et al, 2000).

The ratio of different muscle fibres in a muscle, or in an individual, defines what kind of work it will be able to cope with. Skeletal muscle tissue is very dynamic and easily adapts to change. By changing the kind of exercise or by shifting the workload up or down, muscle tissue has the ability to adjust the ratio of fibres according to its needs in order to be able to cope better (Pette et al, 2000).

Enduring exercise is proven to induce a transition of muscle fibres from fast to slower type; on the contrary absence of muscular work can convert muscle fibres from slow to fast muscle fibres, i.e. the more work a muscle has to do the more work it will eventually be able to cope with (Pette et al, 2000). Extreme workload on the muscle can make the fibres switch from slow to the more powerful fast type (Rockl et al, 2007). Thyroid hormones and age are other factors, which influence fibre type transition (Pette et al, 2000).

AMP-ACTIVATED PROTEIN KINASE

In order to be able to discuss the relevance of cAMP in fibre transition, one has to consider mechanisms at a cellular level. Transcription, translation and proteolysis alternation can be initiated by the steps which convert ATP to cAMP, outlined in earlier chapters (Pette et al, 2000). The process of which is mediated by adenylyl cyclase as a response to G-protein binding, and the resulting protein kinase (AMPK) as the subsequent effect (Sjaastad et al, 2010). The biological responses of which create an impact on the physiological functions of the muscle. Muscle contractions serve as external stimuli and initiate the entire cascade (Sakamoto et al, 2005).