Muscle Excitation

• Muscle excitation begins with the diffusion of calcium ions.
    - Calcium ions diffuse into the axon terminal due to a change in membrane potential.
    - The membrane of the axon terminal contains voltage-gated calcium channels.
    - These channels open in response to an action potential.
    - Consequently, calcium ions are permitted to diffuse into the cell.

Neurotransmitter Release

• Acetylcholine Release
    - Within the axon terminal, there are membrane-bound synaptic vesicles that contain the neurotransmitter acetylcholine.
    - The influx of calcium ions causes these vesicles to release acetylcholine into the synaptic cleft.
    - After release, acetylcholine binds to receptors located on the postsynaptic side of the synaptic cleft.
    - The junctional folds, which are structures of the postsynaptic membrane, contain acetylcholine receptors.
    - These receptors are chemically gated ion channels.
    - Upon binding to acetylcholine, these channels open, leading to excitation of the muscle fiber.

Excitation-Contraction Coupling

• The excitation-contraction coupling process includes the following key steps:
    - The action potential is initiated on the adjacent sarcolemma.
    - This action potential must be conducted across the entire muscle fiber, facilitated by voltage-gated sodium channels in the sarcolemma.
    - T-tubules also contain voltage-gated channels that release voltage-gated proteins and calcium release channels.
    - The opening of these channels allows calcium ions from the sarcoplasmic reticulum (SR) to enter the sarcoplasm (the cytoplasm of a muscle cell).
    - Calcium ions activate the sarcomeres of each myofibril, which are the fundamental units of muscle contraction.

Preparation for Power Stroke

• Binding Dynamics of Actin & Myosin
    - Each actin filament contains a binding site for myosin heads; however, these sites are covered by tropomyosin in the absence of calcium.
    - When calcium ions are released from the terminal cisterns, they bind to troponin.
    - This binding causes a conformational change in troponin, leading to movement of tropomyosin away from actin's binding sites.
    - Once binding sites are exposed, myosin heads can attach to form cross-bridges between thick and thin filaments.

Contraction Process

• Crossbridge Formation
    - The binding of myosin heads to actin initiates the contraction process.
    - When calcium is present, it triggers troponin's action to allow binding, facilitating the power stroke.
    - The power stroke begins from a high-energy state, when myosin heads are bound to ADP and inorganic phosphate (Pi).
    - The energy released from ADP-Pi enables the myosin heads to pivot, pulling thin filaments towards the center of the sarcomere.

• Myosin Power Stroke
    - The myosin head comprises two key portions:
      - Hinge Portion: Enables the head to pivot and reach the binding site on actin.
      - The pivoting head can switch between high and low energy configurations during the power stroke.
    - Upon completion of the power stroke, ADP is released, and myosin enters a low-energy state.

Crossbridge Detachment

• Detachment Mechanism
    - Myosin remains attached to actin until ATP binds to the myosin head.
    - The binding of ATP weakens the attachment between actin and myosin, allowing the myosin head to detach.
    - Following detachment, the myosin head remains in a low-energy state until it is re-energized.

Relaxation Phase

• Calcium Ion Reabsorption
    - The terminal cisterns of the sarcoplasmic reticulum cease releasing calcium ions due to a halt in motor neuron signaling.
    - No additional action potentials are conducted along the sarcolemma.
    - Calcium ions are actively transported out of the sarcoplasm and back into the sarcoplasmic reticulum through calcium pumps.
    - This process reduces the concentration of calcium in the sarcoplasm below the threshold required for excitation-contraction coupling.

• Role of Troponin and Tropomyosin
    - As calcium concentration decreases, troponin returns to its original state.
    - Tropomyosin then glides back over the binding sites on actin.
    - Even if myosin heads remain in a high-energy state, they can no longer form cross-bridges.
    - The sarcomeres return to their original length as the muscle relaxes.