The Steps of Skeletal Muscle Contraction
Skeletal muscle contraction is necessary for locomotion. The sarcomere is the functional unit of contraction. Myofibrils are made of repeating sarcomeres (along the length of the fibril). Many myofibrils make up a muscle fiber, or myocyte.
A network of fluid-filled tubes, called T-tubules, surrounds the myofibrils. These tubes open into the sarcolemma, or the plasma membrane of the myocyte. Therefore, T tubules are continuous with the extracellular environment.
When acetylcholine (ACh) is released from a motor neuron into the neuromuscular junction (NMJ), the muscle’s motor end plate ACh receptors are activated. ACh receptors in the body can either be metabotropic (as in muscarinic receptors) or ionotropic (as in nicotinic receptors). In the muscular system, only ionotropic (nicotinic) receptors are present. As a result, ACh receptor activation at the NMJ results in membrane depolarization via rapid cation entry at the motor end plate.
Pictured is the neuromuscular junction.
1 is the axon of the motor neuron innervating the muscle fiber. 3 is a vesicle filled with ACh. 2 is the plasma membrane of the fiber. 4 is an ACh receptor embedded in the muscle fiber’s plasma membrane. 5 is pointing at a structure in the interior of the muscle fiber. (I pulled this image from Wikipedia, and I’m not entirely sure why the image is pointing towards the mitochondria. Maybe ACh acts on the muscle’s mitochondria somehow. I’m not sure.)
This local depolarization increases in magnitude as more ACh receptors are stimulated over time. Depolarization begins to spread through the T tubules in order to reach the central myofibrils of the myocyte. The dihydropyridine receptor (DHPR) is embedded in the lining of the T tubule, where it functions as a cation sensor. Once activated by depolarization, the DHP receptor stimulates the adjacent ryanodine receptor (RyR). The RyR induces opening of the sarcoplasmic reticulum (SR), which stores Ca2+. The resulting spike in Ca2+ concentration is necessary for sarcomeric movement.
The spike in Ca2+ is quickly curbed when the Ca2+ ATPase in the SR membrane actively transports Ca2+ back into the SR. This prevents muscular tetanus, in which a high frequency of motor neuron action potentials causes increased rate of muscle contractions, which compound onto each other and fuse into one tetanic contraction. To prevent this, the ATPase brings Ca2+ back into the SR to decrease concentration of Ca2+ and thus lower frequency of muscle contraction.
Ca2+ is necessary for the sliding filament mechanism, which facilitates cross-bridge cycling, to take place. Pictured below is the filament structure that makes a sarcomere.
When the sarcomere is stationary, the myosin heads (protruding from the thick filament) do not have access to the actin binding sites (on the thin filament) because of tropomyosin blockage. Ca2+ complexes with troponin to unravel tropomyosin from actin, allowing myosin heads to attach to actin sites.
The method by which actin and myosin interact to cause muscle contraction is best explained in the context of the power stroke, which requires cytosolic ATP as an energy source. The following are the steps of the sliding filament mechanism:
ATP, bound to the myosin head, is hydrolyzed into ADP and a phosphate group (denoted Pi).
ATP hydrolysis releases adequate energy for the myosin head to cock and bind to the thin filament.
The myosin heads, attached to actin, slide back into their original position passively, because their original position was more favorable.
Another ATP molecule is necessary for the myosin head to detach from the actin filament.
This ATP molecule is then hydrolyzed, as in step 1, and the cycle repeats.
This is how muscle contraction works, from stimulus to response. Here are some cool sources if you are interested in learning more about muscle contraction:
https://www.youtube.com/watch?v=7_LZFmfeCuk - Great video explaining the basics of muscle anatomy and the sliding filament mechanism.
https://www.ncbi.nlm.nih.gov/books/NBK526134/ - An article delving into the differences between nicotinic and muscarinic ACh receptors.
https://pubmed.ncbi.nlm.nih.gov/12508050/ - An article describing a newly discovered role of the DHP receptor in Ca2+ dependent cellular signaling.
