Muscle Membrane, T Tubules, and Sarcoplasmic Reticulum

T tubules are specialized invaginations of the sarcolemma, with which it is continuous at multiple points. T tubules run transverse to the muscle fibers themselves and the sarcolemma and encircle individual muscle fibrils. T tubules form deep invaginations into the sarcolemma. This provides not only more rapid dispersal of muscle membrane depolarization along the muscle fiber, but it allows for propagation along both the surface of the sarcolemma and into the muscle fiber, where it can interact with deep sarcoplasmic reticulum. T tubules interact directly with components of the sarcoplasmic reticulum, leading to Ca²⁺ release into the sarcoplasm. They also harbor voltage-gated Ca²⁺ channels, L-type Ca²⁺ channels. These Ca²⁺ channels do not contribute to depolarization or the muscle fiber action potential but, rather, act as voltage sensors of muscle membrane depolarization. The sarcoplasmic reticulum forms a network of tubules surrounding muscle fibrils inside the sarcolemma.

Junctional sarcoplasmic reticulum (the terminal cisternae) stores Ca²⁺ and is the site of Ca²⁺ release in response to a muscle fiber action potential. Junctional sarcoplasmic reticulum contains high amounts of calsequestrin, which binds to Ca²⁺ and accounts for the high Ca²⁺ storage of the sarcoplasmic reticulum. The sarcoplasmic reticulum is so efficient in this role that the muscle fiber loses very little Ca²⁺ even after repeated muscle contractions. Junctional sarcoplasmic reticulum is also the site of the Ca²⁺ channel responsible for releasing large stores of calcium into the sarcoplasm, the ryanodine receptor, so named for its binding to the plant alkaloid ryanodine.

Sarcoplasmic reticulum voltage-gated Ca²⁺ channels sense the depolarization of the T tubule, interact directly with the ryanodine receptor and induce it to release Ca²⁺ from the sarcoplasmic reticulum. Free sarcoplasmic reticulum constitutes the remainder of the intrafiber sarcoplasmic reticulum membrane system. It is not associated with the T tubule system and functions in Ca²⁺ reuptake into the sarcoplasmic reticulum. It has a large number of Ca²⁺ adenosine triphosphatase (ATPase) pumps on its surface that function in the energy-dependent reuptake of sarcoplasmic Ca²⁺ and therefore plays a role in muscle relaxation rather than excitation and contraction.

A motor nerve action potential propagates down the motor nerve axon to the nerve terminal, causing release of acetylcholine (ACh) into the synaptic cleft of the neuromuscular junction. After binding of acetylcholine to the postsynaptic muscle membrane acetylcholine receptor (AChR), there is generation of an end-plate potential. Suprathreshold end-plate potentials generate muscle fiber action potentials. These propagate along the sarcolemma, depolarizing the muscle membrane sequentially as it travels along the membrane. The action potential continues down the T tubules. Depolarization of the T tubule membrane activates the voltage-gated Ca²⁺ channel, thus activating the ryanodine receptor, releasing large amounts of Ca²⁺ from the sarcoplasmic reticulum into the sarcoplasm. This leads to cross-bridge formation between thin and thick filaments, activation of the cross-bridge cycle, sliding of the thick and thin filaments past one another, sarcomere shortening, and eventually muscle contraction. Energy-dependent Ca²⁺ reuptake into the sarcoplasmic reticulum assists in relaxation and replenishes the supply of Ca²⁺ ready for release after the next depolarization.