Skeletal muscle structure and function
2.2 Muscle contraction
Having outlined basic skeletal muscle structure, it is now appropriate to move onto the process of muscle contraction. When students begin to study this process, they often neglect the importance of the central nervous system and instead become more engrossed in the peripheral mechanisms of muscle contraction (Morton et al., 2008). How- ever, it is important to note that voluntary muscle contractions begin with a nerve impulse travelling from the motor cortex in the brain through to the spinal cord via the brain stem. As outlined in the Section 2.1, the neural impulses are then commu- nicated to skeletal muscle fibres through the action of the motor neurons which branch out from the spinal cord (see Figure 2.7).
2.2.1 Propagation of the action potential In order for muscle fibres to contract, an action potential needs to be generated and must propa- gate along the surface of the fibre and deep into the interior of the fibre. This action potential is generated according to a series of events at the NMJ, as described below and shown in Figure 2.8:
1. Release of ACh.When the nerve impulse arrives at the synaptic end bulbs, it causes the synaptic vesicles to fuse with the plasma membrane of the motor neuron. As a result, ACh is subse- quently released into the synaptic cleft, where it can diffuse across the space between the motor neuron and motor end plate.
2. Activation of ACh receptors and production of action potential.The ACh receptors function as
voltage-gated ion channels which become active upon binding of two ACh molecules. As soon as binding has occurred, the ion channel opens, causing a flow of Na+ into the muscle fibre and efflux of K+. However, Na+ influx exceeds K+ efflux because the electrochemical driving force is greater for Na+. As a result, the interior of the fibre becomes positively charged, thus depo- larizing the plasma membrane. It is this change in membrane potential which triggers the action potential, which then propagates along the sar- colemma and into the T-tubules.
3. Termination of ACh activity. ACh is rapidly degraded by the enzyme acetylcholinesterase (AChE), an enzyme which is attached to collagen fibres in the extracellular matrix of the synaptic cleft. For this reason, a continual production of muscle action potentials is needed in order for contractions to be sustained.
2.2.2 Excitation-contraction coupling
The process of excitation-contraction (EC) cou- pling collectively refers to those stages which connect muscle excitation (i.e. propagation of an action potential) through to muscle contraction itself (i.e. generation of force). While there are various steps in this process, the release of Ca2+
from the sarcoplasmic reticulum is an integral component. Calcium is stored in the SR in millimolar concentrations (at approx 10 mM), whereas its concentration in the sarcoplasm is 10,000 times lower (i.e. 0.1µM).
The release of calcium is essentially under- pinned by the conversion of an electrical signal into a chemical signal, and it requires the presence of two key membrane proteins. When the action potential has travelled into the T-tubules, it causes a conformational change in the voltage sensing type channel known as thedihydropyridine(DHP) receptor. This change in DHP receptors, in turn, opens the calcium release channels in the SR, the ryanodine receptors (RyR). Calcium then flows down its electrochemical gradient, signalling the contractile apparatus to contract according to the sliding filament mechanism (see Figure 2.8).
Axon collateral of somatic motor neuron
Axon terminal Synaptic end bulb Neuromuscular junction (NMJ)
(a) Neuromuscular junction
(b) Enlarged view of the neuromuscular junction
(c) Binding of acetylcholine to ACh receptors in the motor and plate
(d) Neuromuscular junction
Axon terminal Nerve impulse Synaptic vesicle containing acetylcholine (ACh) Synaptic end bulb Synaptic cleft (space)
Synaptic end bulb
ACh is broken down
Motor end plate
Muscle action potential is produced
Axon terminal Synaptic end bulbs
Skeletal muscle fiber
SEM 1650x Sarcolemma
ACh in released from synaptic vesicle
ACh binds to ACh receptor
Junctional fold
Blood capillary Axon collateral (branch)
Axon collateral
Synaptic end bulbs Somatic motor neuron Synaptic cleft (space) 1
4
3 2
Sarcolemma
Motor end plate
Myofibril
Figure 2.6 The neuromuscular junction (NMJ). (From Tortora and Derrickson,Principles of Anatomy and Physiology, Twelfth Edition, 2009, reproduced by permission of John Wiley & Sons Inc.)
Planning of willed movements
Motor cortical &
other corticospinal outputs
motor axons
neuromuscular junction
& sarcolemma
excitation-contraction coupling
cross-bridge force ATP hydrolysis
Other supraspinal
& propriospinal outputs
α and γ motor neurons
Figure 2.7 Simplified schematic of the chain of events from brain to muscle which result in force production.
(adapted from Gandevia, 2001)
Note that the calcium needs to be pumped back into the SR so that it is again available to signal the contractile proteins upon the next delivery of an action potential. As noted earlier, the SR pumps calcium back into its lumen in an ATP-requiring process through the action of sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) (Periasamy &
Kalyanasundaram, 2007).
2.2.3 The sliding filament mechanism
At a molecular level, muscle contraction can be explained by the sliding filament mechanism. Essentially, this process involves the binding of myosin heads to actin filaments. By way of the action of sliding over each other, the actin filaments are then pulled towards the M-line.
As a result, the overall length of the sarcomere shortens and hence the muscle fibre contracts.
In a relaxed muscle, however, myosin is prevented from binding to actin because the
protein tropomyosin is wrapped around the actin filaments, thus covering the actin-myosin binding site. The positioning of tropomyosin is, in turn, held in place via three related proteins which we will collectively refer to as troponin (though in the instance of muscle contraction we are specifically concerned with the troponin C protein). When Ca2+ is released into the cytosol, it binds to troponin C, which then causes the troponin- tropomyosin complex to move away from the binding site. Upon exposure of the myosin binding site, the series of events comprising the contraction-relaxation cycle can begin.
Let’s look at the four events comprising this cycle in more detail now and as outlined in Figure 2.9:
1. ATP hydrolysis. The myosin head binds ATP, and the enzyme myosin ATPase then hydrolyzes ATP into ADP and a phosphate group. The products of this reaction are still attached to the myosin head.
2. Crossbridge formation. As a result of ATP hydrolysis, the myosin head becomes energized and attaches to the binding site on the actin filament to form crossbridges. Upon binding, the phosphate group is released.
3. Power stroke. Upon the release of the phos- phate group, the myosin head tilts and rotates on its hinge in a movement known as thepower stroke. As a result of the rotation, the myosin head generates forces and pulls the actin fila- ments towards the centre of the sarcomere via the sliding filament mechanism, whereby the thin and thick filaments slide over one another.
As a consequence of the actin filaments sliding towards the M-line, it is important to note that it is the I-band which shortens during contraction, whereas the A-band does not change length (see Figure 2.10). The stages of the power stroke can be likened to walking, in that each myosin head is essentially ‘walking’ along the actin fil- aments, ultimately getting closer and closer to the Z-disc. In turn, the actin filaments are being pulled towards the M-line.
4. Detachment of myosin from actin.At the end of the power stroke, the myosin then releases ADP
and myosin remains bound to actin until the next supply of ATP binds to myosin. Upon ATP binding, myosin then becomes released and the contraction cycle can begin again when ATPase hydrolyzes ATP.
In order for the above events to occur, it is important to appreciate that there needs to be a continual supply of ATP and Ca2+. Depending on the particular contractile conditions (e.g. intensity and duration), the continual production of ATP can be provided from high-energy phosphates and/or the metabolism of carbohydrate, fat or protein, as introduced in Chapter 1. Part 2 will outline the basic biochemical pathways involved in these processes and, in Part 3 we will examine the regu- lation of these pathways during different types of sports and exercise.