MUSCLE CONTRACTION
Muscle contraction is a complex phenomenon involving the coordinated interaction between motor neurones and muscle fibres. Each muscle fibre is connected to multiple terminal branches of motor neurons, creating motor units that can vary in size.
The size of each motor unit is unique and determined by the number of muscle fibres that are innervated by the terminal branches of the motor neurons. The larger motor units in the limbs and postural muscles are characterised by a single axon providing multiple muscle fibres. In contrast, the smaller motor units, linked with eye movements, have a single axon that may only offer a few muscle fibres.7.4.1 Excitation Contraction Coupling
The point of contact between the end of a motor neurone and a muscle fibre is known as the neuromuscular junction. This junction serves as a connection between the two. Although the axon’s terminal branch does not directly touch the muscle fibre, it communicates with it through a gap called the synaptic cleft. The neurotransmitter acetylcholine (ACh) is stored in vesicles within the axon’s terminal branch, waiting to be released into the synaptic cleft when a signal arrives.
When an action potential arrives at the neuromuscular junction, it triggers the opening of voltage-gated Ca2+ and Na+ channels, causing an influx of calcium ions into the axon’s terminal bulb. The DHP receptors, also known as voltage-gated Ca2+ channels, can be hindered by antihy- pertensive/antiarrhythmic drugs belonging to the class of Ca2+ channel blockers. The ryanodine receptors, also known as Ca2+ release channels, on the other hand, can be activated by caffeine. This rapid increase in calcium ion concentration of around 10 to 100 times triggers the binding of synaptic vesicles to the terminal bulb’s plasma membrane, allowing the release of ACh into the synaptic cleft. The ACh diffuses into the muscle fibre sarcolemma’s invaginations, binding to ACh receptors and initiating the process of depolarisation (Figure 7.9).
The enzyme acetylcholinesterase (AChE) hydrolyses ACh into acetic acid and choline almost immediately after its release. For the next action potential to be propagated to the muscle fibre, a new action potential at the neuromuscular junction must occur. AChE is found in high concentrations within the small size of the synaptic cleft. This, along with the limited diffusion distance of ACh in the synaptic cleft, accounts for the speedy hydrolysis of ACh.
Ach Receptor: The acetylcholine receptor is a key nervous system component, playing a crucial role in transmitting signals between nerve cells. It is a type of protein known as an ion channel, which forms a pathway across the cell membrane for ions to move in and out of the cell. The structure and function of the acetylcholine receptor are complex and finely tuned to allow for precise control over these ion movements. The receptor comprises five subunits, arranged in a ring to form a channel through the cell membrane. In foetuses, these subunits are two alpha, one beta, one delta, and one gamma. However, in adults, an epsilon subunit replaces the gamma subunit. Each of these subunits contributes to the overall structure and function of the receptor. The channel is normally narrow but can change shape and open when two acetylcholine molecules bind to the alpha subunits. This opening allows ions to pass through the channel. The channel is about 0.65 nanometres wide when open, which is large enough for positive ions like sodium (Na+), potassium (K+), and calcium (Ca2+) to pass through easily. Patch clamp studies, a type of experiment used to measure the movement of ions through individual channels, have shown that an open acetylcholine receptor channel can allow 15,000 to 30,000 sodium ions to pass in just one millisecond. This rapid movement of ions allows nerve cells to transmit signals quickly and efficiently. However, not all ions can pass through the acetylcholine receptor channel. Negative ions such as chloride are repelled and cannot pass through due to the negative charges at the channel’s entrance.
This selectivity is essential for maintaining the balance of ions inside and outside the cell, which is crucial for the proper functioning the nervous system.7.4.2 Unloading of Calcium for
Initiating Contraction
The depolarization propagates in all directions from the neuromuscular junction centrally located on the muscle fibre, starting with the T tubules. The T tubules act as communication links between the sarcolemma and the myofibrils within each muscle fibre. When a stimulus is received, the depolarisation continues in the T tubules, releasing calcium ions from the sarcoplasmic reticulum into the muscle fibre’s cytosol, allowing the contraction to begin. With the entry of calcium ions, myosin filaments get attracted to unexposed active sites of actin filaments, allowing them to slide over each other, resulting in the reduction of sarcomere length. Just milliseconds after muscle contraction, the calcium membrane pump pumps calcium ions back into the sarcoplasmic reticulum, leading to the stoppage of muscle contraction.
7.4.3 Ratchet Theory of Muscle Contraction
or Sliding Mechanism
The ratchet theory, also known as the walk-along theory or the sliding mechanism, provides a comprehensive framework for understanding the interaction between the activated actin filament and myosin cross-bridges during muscle contraction. When calcium ions activate the actin filament, the myosin cross-bridge heads are attracted to the active sites of the actin filament, initiating the contraction process. This theory describes the stepwise process of the myosin cross-bridges attaching to and disengaging from the active sites of the actin filament. When a myosin head attaches to an active site, it causes profound changes in the intramolecular forces between the head and arm of the cross-bridge, leading to a power stroke where the head tilts and drags the actin filament (Figure 7.10).
This process is repeated as the myosin cross-bridges stretch the actin filament, pulling actin filaments of two different ends toward the centre of the myosin filament or to the H zone.
Each myosin cross-bridge is believed to operate independently; in a continuous cycle, there is a repeated process of attaching and pulling the actin filaments. The force of contraction is directly proportional to the number of myosin cross-bridges that are in touch with the actin filament at a particular moment. This theory provides valuable insights into the molecular events that underlie muscle contraction, shedding light on the coordinated interplay between the actin and myosin filaments. It is supported by considerable evidence and is a fundamental concept in muscle physiology. The walk-along theory has been a subject of extensive research, and recent studies have provided further evidence supporting its fundamental principles. Advanced imaging techniques, such as high-speed atomic force microscopy, have allowed researchers to directly observe the structural changes in myosin and actin filaments during the contraction process, providing visual confirmation of the mechanisms proposed by the walk-along theory. Additionally, studies utilising genetic and biochemical approaches have further elucidated the role of specific molecular components in the cross-bridge cycling process, supporting the independent and coordinated action of myosin cross-bridges during muscle contraction.7.5