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Neuromuscular Junction And Whole Muscle Contraction

Neuromuscular Junction And Whole Muscle Contraction
Neuromuscular junction
For skeletal (voluntary) muscle to contract, there must be neuronal activation to the muscle fibres themselves from either higher centres in the brain or via reflex pathways involving either the spinal cord or the brain stem. The neurones that innervate skeletal muscles are called α-motor neurones. Each motor axon splits into a number of branches that make contact with the surface of individual muscle fibres in the form of bulb-shaped endings. These endings make connections with a specialized structure on the surface of the muscle fibre, called the motor end plate, and together form the neuromuscular junction (NMJ) (Fig. 13a).

The role of the NMJ is the one-to-one transmission of excitatory impulses from the α-motor neurone to the muscle fibres it innervates. It allows a reliable transmission of the impulses from nerve to muscle and produces a predictable response in the muscle. In other words, an action potential in the motor neurone must produce an action potential in the muscle fibres it innervates; this, in turn, must produce a contraction of the muscle fibres. The process by which the NMJ produces this one-to-one response is shown in Figures 13a and b.

The motor neurone axon terminal has a large number of vesicles containing the transmitter substance acetylcholine (ACh). At rest, when not stimulated, a small number of these vesicles release their contents, by a process called exocytosis, into the synaptic cleft between the neurones and the muscle fibres. ACh diffuses across the cleft and reacts with specific ACh receptor proteins in the postsynaptic mem- brane (motor end plate). These receptors contain an integral ion channel, which opens and allows the movement inwards (influx) of small cations, mainly Na+. There are more than 107 receptors on each end plate (postjunctional membrane); each of these can open for about 1 ms and allow small positively charged ions to enter the cell. This movement of positively charged ions generates an end plate potential (EPP). This is a depolarization of the cell with a rise-time of approximately 1–2 ms and may vary in amplitude (unlike the all- or-nothing response seen in the action potential; Chapter 6). The random release of ACh from the vesicles at rest gives rise to small, 0–4-mV depolarizations of the end plate, called miniature end plate potentials (MEPP) (Fig. 13c).

However, when an action potential reaches the prejunctional nerve terminal, there is an enhanced permeability of the membrane to Ca2+ ions due to opening of voltage-gated Ca2+ channels. This causes an increase in the exocytotic release of ACh from several hundred vesicles at the same time. This sudden volume of ACh diffuses across the cleft and stimulates a large number of receptors on the postsynaptic membrane, and thus produces an EPP that is above the threshold for triggering an action potential in the muscle fibre. It triggers a self- propagating muscle action potential. The depolarizing current (the generator potential) generated by the numbers of quanta of ACh is more than sufficient to cause the initiation of an action potential in the muscle membrane surrounding the postsynaptic junction. The typical summed EPP is usually four times the potential necessary to trigger an action potential in the muscle fibre, and so there is a large inherent safety factor.
The effect of ACh is rapidly abolished by the activity of the enzyme acetylcholinesterase (AChE). ACh is hydrolysed to choline and acetic acid. About one-half of the choline is recaptured by the presynaptic nerve terminal and used to make more ACh. Some ACh diffuses out of the cleft, but the enzyme destroys most of it. The number of vesicles available in the nerve ending is said to be sufficient for only about 2000 nerve–muscle impulses, and therefore the vesicles reform very rapidly within about 30 s (Fig. 13b).

Neuromuscular Junction And Whole Muscle Contraction

Whole muscle contraction
As the action potential spreads over the muscle fibre, it invades the T-tubules and releases Ca2+ from the sarcoplasmic reticulum into the sarcoplasm, and the muscle fibres that are excited contract. This contraction will be maintained as long as the levels of Ca2+ are high. The single contraction of a muscle due to a single action potential is called a muscle twitch. Fibres are divided into fast and slow twitch fibres depending on the time course of their twitch contraction. This is determined by the type of myosin in the muscles and the amount of sarcoplasmic reticulum. Different muscles are made up of different proportions of these two types of fibre, leading to a huge variation in overall muscle contraction times (Fig. 3d).
At rest, muscles exert tension when stretched. Muscles have a passive elastic property and act both in series and parallel to the contractile element (Fig. 13e).
Isometric contraction occurs when the two  ends  of  a  muscle are held at a fixed distance apart, and stimulation of the muscle causes the development of tension within the muscle without a change in muscle length. Isotonic contraction occurs when one end of the muscle is  free  to  move  and  the  muscle  shortens  whilst  exerting a constant force. In practice, most contractions are made up of both elements.
The relationships between resting, active and total tensions developed in skeletal muscle are shown in Figure 13f. The passive curve is due to the stretching of the elastic components, the active curve is due to contraction of the sarcomeres alone (contractile component), and the total curve is due to the sum of the passive and active tensions developed. It can be seen that the active tension developed is dependent on the length of the muscle. The optimum length occurs where the thick and thin filaments are thought to provide a maximum number of active cross-bridge sites for interaction (this length is very close to that of the resting length of a particular muscle). As the muscle length is increased, the thick and thin filaments overlap less, providing fewer cross-bridge sites for interaction; as the muscle shortens below the optimal length, the thin filaments overlap one another and, in so doing, reduce the number of active sites available for interaction with the thick filaments.