We have discussed what makes muscles contract. We next consider when they contract. Skeletal and smooth muscle fibers are both activated by the nervous system. Whereas vertebrate skeletal muscles are innervated by the somatic nervous system, smooth muscles are innervated by the autonomic nervous system, as are cardiac muscles (Chapter 35).

Like nerve cells, muscle fibers are electrically excitable. Skeletal muscle fibers are activated by impulses transmitted by motor nerves to synaptic junctions (Fig. 37.8). Motor neuron axons have branches that allow them to synapse with multiple muscle fibers. When action potentials traveling down a motor neuron arrive at the neuromuscular junction, the neurotransmitter acetylcholine is released into the synaptic cleft. The neurotransmitter binds with postsynaptic receptors on the muscle cell at a region called the motor endplate, triggering the opening of Na+ channels. The resulting influx of Na+ ions in turn initiates a wave of depolarization that passes from the neuromuscular junction toward both ends of the muscle fiber (Chapter 35).

How does membrane depolarization lead to the cross-bridge cycle? Actin and myosin filaments can form cross-bridges only when the myosin-binding sites on actin are exposed. At rest, these binding sites are blocked by the protein tropomyosin. The wave of depolarization in the muscle cell initiates a chain of events that moves tropomyosin away from these binding sites, allowing cross-bridges between actin and myosin to form and the muscle to contract (Fig. 37.8).

Let’s look at the chain of events that concludes with the exposure of the myosin-binding sites in more detail. You saw in Chapter 5 that eukaryotic cells contain several types of membrane-bound internal organelle. The myofibrils of muscle cells are surrounded by a highly branched membrane-bound organelle called the sarcoplasmic reticulum (SR), a modified form of the endoplasmic reticulum (Fig. 37.8). Depolarization initiated in the plasma membrane is conducted to the SR through infoldings of the plasma membrane (Fig. 37.8). When the muscle is at rest, the SR contains a large internal concentration of calcium (Ca²⁺) ions transported in by calcium pumps in its membranes.

A muscular contraction is initiated when depolarization of the muscle fiber causes the SR to release Ca²⁺. The Ca²⁺ diffuses into the myofibrils and binds to a protein called troponin, causing the troponin molecule to change shape. This conformational change of troponin, in turn, causes tropomyosin to move, exposing myosin-binding sites along the actin filament. Now myosin cross-bridges can form with actin, producing a contraction. Note that at this stage in the cross-bridge cycle, the myosin head has already hydrolyzed ATP, is bound to ADP and P_i, and is in the cocked-back “ready” position. Binding to actin then allows the power stroke to occur. In this way, contraction is initiated immediately following depolarization and release of Ca²⁺.

792

The process by which membrane depolarization leads to Ca²⁺ release from the SR and the formation of myosin-actin cross-bridges is called excitation–contraction coupling because excitation of the muscle cell is coupled to contraction of the muscle, producing force and movement. Together, these events are the molecular “switch” that causes a muscle to contract. The muscle relaxes when neural stimulation ends. Acetylcholine is broken down or reabsorbed, and Ca²⁺ is actively transported back into the sarcoplasmic reticulum, allowing tropomyosin molecules to once again block myosin-binding sites along the actin filaments.

Quick Check 2 Curare is a paralyzing compound that blocks the action of the neurotransmitter acetylcholine at the muscle fiber’s motor endplate. What effect do you think curare has on the release of calcium ions from the sarcoplasmic reticulum of the muscle cell?