The period of muscle contraction primarily influences the duration of stimulation at the neuromuscular junction (NMJ), the presence of free calcium ions in the sarcoplasm, and the availability of energy or ATP to support contractions.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open. Calcium ions entering the cell initiate a signaling cascade that causes small membrane-bound vesicles, called synaptic vesicles, containing neurotransmitter molecules to fuse with the presynaptic membrane. The fusion of a vesicle with the presynaptic membrane causes neurotransmitters to be released into the synaptic cleft, the extracellular space between the presynaptic and postsynaptic membranes.
A single action potential reaching the presynaptic end of the neuromuscular junction triggers the release of acetylcholine in the synaptic cleft. Once the receptors present on the postsynaptic membrane recognize acetylcholine, the neurotransmitter quickly dissociates from the receptor and is degraded by acetylcholinesterase present in the synaptic cleft. The swift removal and inactivation of acetylcholine from the receptor prevent overstimulation of the postsynaptic membrane from excessive firing of action potentials. As a result, the muscle membrane repolarizes, and the calcium concentration in the muscle fiber returns to a normal resting level. There are two mechanisms involved in restoring normal intracellular calcium levels: the active transport of calcium into the sarcoplasmic reticulum (SR) and of calcium across the sarcolemma into the extracellular fluid. Of the two mechanisms, the transport into the SR is more important. The SR promptly resumes normal permeability and actively reabsorbs calcium ions from the surrounding cytosol. When calcium concentration in the cytosol decreases, the contraction process reverses. Troponin releases calcium ions and reverts to its original conformation. As a result, the tropomyosin moves back, covering the myosin-binding sites on actin. Therefore, a single action potential only has a brief impact on the muscle fiber.
When there is a rapid succession of action potentials at the presynaptic end of the neuromuscular junction, there is a continuous release of acetylcholine. This, in turn, triggers a series of action potentials in the sarcolemma at the post-synaptic end and results in continuous high levels of calcium in the cytosol. Under these circumstances, the contraction cycle repeats itself without muscle fibers undergoing relaxation.
