10.1 The Physiological Actions Implementing Movement – Contraction of Muscles

What constitutes muscle cells and their contractile elements?

To reach our goal here, it is important to envision the whole and the functional system we’re discussing. Neural signals need to be sent from their sources in the spinal cord or brainstem out to merge with sets of skeletal muscles where these neurons release neurotransmitter and engage contractions. Neurotransmitter release happens at the terminals of these motoneurons, where it then binds to receptors at distinct locations constituting “the muscle.” This binding initiates a cascade of events that leads to muscle contraction, garnering different amounts of force as needed for actions. This phenomenon involves the actions of several players whose names and roles will now be more specifically delineated. Knowing the players will help to understand how the team wins desired actions with intelligent sophistication.

The individual muscle cell is called a muscle fiber, or myofiber. Myofibers arrange themselves in parallel to add cooperative force, or in series (connected end-to-end) to provide length so contraction velocity can build, by accumulating themselves between tendon attachments. Figure 10.2 shows how a muscle mass is composed of multiple muscle fibers (arranged in parallel or series).

Figure 10.2 Muscle to sarcomere

Individual myofibers can be several centimeters in length and are typically about 80μm in diameter. Each myofiber or muscle fiber contains multiple myofibrils. Myofibrils are elongated rods composed of repeating patterns of proteins. These proteins provide the basis of contraction due to being made up of components that can be induced by the cascade following neurotransmitter receptor activation to pull against each other, shrinking the internal mass, and pulling connected body parts closer together. The more myofibrils packed into a muscle fiber, the more force that muscle fiber can produce. The repeating protein patterns of myofibrils create darker and lighter bands that are visible when looking at muscles. Therefore, skeletal muscles are called "striated."

Within the bundles of myofibrils, the repeating protein patterns represent multiple contractile units called sarcomeres. Several sarcomeres repeat in series along the length of a myofiber. The lower half of Figure 10.2 shows how each sarcomere is bounded on the outside by a Z-disk, into which the tail ends of actin "thin" filaments embed, holding them tightly. Actin are composed of actin protein monomers strung together and wrapped around each other in double helixes. At each full cycle along the helix of each actin filament, there resides a binding site for myosin that is typically covered by tropomyosin, which is a long filamentous peptide chain following the actin helix around each curve.

The actin/tropomyosin filaments make up the "thin filaments" of the sarcomere. Between the protruding strands of actin/tropomyosin, in a separate bundle held in place by the M-line in the middle of the sarcomere and thin strands of titin at either end, there are bunches of outward-facing myosin. These bundles end up with globular heads of myosin bulging out from the bundle at regular small intervals. The remaining portions of myosin are buried in a way that appears like twisted microscopic grape vines (fiber represented by vine, and grapes representing globular heads, middle portion of blowup in Figure 10.2). These myosin bundles extend from the center and comprise "thick" filaments. Finally, along the actin/tropomyosin thin filaments, and at regular intervals near the myosin binding sites, the troponin molecules are found to be attached to both the actin and the tropomyosin (shown in the smaller detail box at the bottom of Figure 10.2).

How does a sarcomere generate contraction?

The basic contraction action of a sarcomere is a repeating cycle in which the myosin heads grab and crawl along the actin/tropomyosin filaments from one binding site to the next, pulling the Z-disks closer together (see Figure 10.3, and watch an animation). This process involves the formation and breakage of cross-bridges between the myosin globular heads and the binding sites along each turn of the actin alpha-helix, initially covered by tropomyosin. To envision how this looks across the sarcomere, imagine the whole thick filament is a caterpillar, its feet lifting from the leaf (actin) and moving forward while others remain planted for stability. While some actin sites are bound by globular myosin heads (caterpillar feet on the leaf), other globular heads are dissociating and thrusting forward to bind again (caterpillar feet lifted off the leaf). This way, the myosin chain pulls actin and its tethered Z-discs inward.

Figure 10.3 Actin myosin contraction cycle

So how is this cycle controlled? Our muscles don't just contract randomly. They contract when our motor neurons tell them to. Calcium is the critical component that controls when this cycle can happen. As described above, myosin grabs on to actin, sticking to binding sites on the actin protein. Without calcium present, those binding sites are blocked by tropomyosin. In response to an upstream action potential in a motor neuron, calcium is released inside the muscle cell. The calcium binds with troponin. Calcium-bound troponin changes shape and acts as a wedge, prying the tropomyosin strand away from the actin strand (Step 2 in Figure 10.3). This shift exposes the myosin binding sites on actin.

Once myosin binds with actin, myosin initiates the "power stroke," changing its shape so as to pull the actin chain toward the center of the sarcomere (Step 3). At the end of the power stroke, an ADP molecule falls off the myosin and an ATP binds to the myosin head instead (Step 4). The ATP binding changes the shape of myosin again, causing it to fall off the actin binding sites (Step 5). When the ATP gets broken back down into ADP + phosphate, the myosin relaxes back to its original position (Step 1). If calcium is present, the cycle can repeat. Though we show this cycle at one specific actin-myosin pair, keep in mind that it occurs throughout the sarcomere, at many sites of potential actin-myosin contact (i.e. the many legs of the caterpillar).

Contractile force entails two distinct processes: shortening and lengthening. This seems counter-intuitive. Isn't "contraction," by definition, "shortening?" Let's clarify by considering the difference between lifting a bowling ball versus catching a bowling ball. The experience of lifting a bowling ball is of course quite different than catching a bowling ball tossed to you. Lifting this ball requires establishing sufficient contractile force to initiate motion upward with muscles in the arms. Catching a bowling ball mostly involves slowing the ball's trajectory or momentum as it moves along rather than immediately reversing its movement. This is where "contractions" differ between shortening (lifting the ball) and lengthening (catching the ball). When the cycling of cross-bridges and power strokes produce sufficient force to counteract a load, muscles can engage shortening contractions and move the limb or body part (we lift the ball). The second category of contraction occurs when contraction force is insufficient to counteract a force, but it can be dampened or slowed down. Often this occurs against the force of gravity, as with the case of catching a bowling ball. The considerable inertia of the heavy bowling ball won't be immediately counteracted by muscle forces in our limbs. Instead, cycling and power strokes produce some counteractive force by attempting to bind and cycle, yet with cross-bridges getting progressively pulled apart like loosening a Velcro seal. These are lengthening contractions. This is analogous to picking up a caterpillar holding on to a leaf, its little legs progressively popping off, slowing your retrieval of the caterpillar. This is important to understand because it describes why some "contractions" seem to be hidden behind the scenes. Like when two muscle-bound competitors are locked in an arm wrestle stalemate, with their gripped hands quivering at the top, one competitor giving a bit (lengthening contraction), with the other gaining a bit (shortening contraction). Similarly, most of our run-of-the-mill movements involve multiple muscles, frequently mixing together shortening and lengthening contractions to achieve our final, desired movement.

From muscle cell action potentials to contractions

Sarcomere contraction relies on a surge of intracellular calcium which is initiated by an action potential that propagates through the muscle fiber. Action potentials of skeletal muscle fibers are initiated by synapsing lower motor neurons (LMNs). LMNs release acetylcholine (ACh) at neuron-muscle synapses called neuromuscular junctions (Figure 10.4 ).

Figure 10.4 Neuromuscular junction Axons of LMNs terminate on muscle fibers in a special synapse called the neuromuscular junction.

The postsynaptic side of these junctions expresses nicotinic ACh receptors, which gate sodium and therefore initiate depolarization when they open. By comparison to CNS neurons which receive thousands of excitatory inputs requiring summation to reach action potential, motoneurons synapse only once with muscle fibers. Thus, both the selection of that fiber contraction and some control over the contractile force, derives from the bolus of acetylcholine (ACh) released upon the fiber. Motoneurons must therefore release large amounts of acetylcholine to ensure enough stimulation of the fiber and cause contraction. Most movement events need to be quick and snappy, and cannot wait for prolonged summation to occur, such as escape from predators.

Figure 10.5 shows how initial sodium influx from ACh receptor activation triggers an action potential in the skeletal muscle. Depolarization of the muscle fiber membrane (sarcolemma) leads to muscle action potentials that are perpetuated across the fiber via voltage-gated sodium channels, much like an action potential travels down an axon (see Chapter 2 Neurophysiology). These sodium-based depolarization waves flash across the muscle fiber membrane and cause calcium release from internal stores in the sarcoplasmic reticulum. This calcium initiates contraction by starting the cycle described above.

Figure 10.5 Neuromuscular junction mechanism

Muscle organization and motor units

The axon of any single motor neuron may branch into several terminals with each forming a synapse on a different muscle fiber. Each muscle fiber, on the other hand, is innervated by a single motoneuron axon. Together, a single motoneuron and the several muscle fibers it communicates with constitute a motor unit (Figure 10.6). Thus, a muscle is composed of many motor units, each of which may involve many muscle fibers. More force can be generated by activating more motor units that contract in a similar direction.

Figure 10.6 Motor unit A motor unit is an alpha motor neuron and all the muscle fibers it synapses on.

To coordinate movement, muscles are activated in pairs of antagonists that pull in opposite directions (flexors or extensors in limbs). Thus, there are ways to coordinate movements by, for example, swinging an arm outward with an extensor and stopping that motion with the opposing flexor. Stiffening any joint requires simultaneously contracting both antagonists surrounding a joint or body part.

Mechanisms of force generation

There are 2 primary ways that we can control how forcefully a muscle contracts (Figure 10.7). The first simple mechanism of force generation derives from stimulation of the same motor unit with higher action potential frequency. This causes a higher number of ACh release events at the neuromuscular junction of all that motor unit's muscle fibers. As these ACh release events occur, they cause repeated bursts of sodium influx at the sarcolemma, which then re-initiates calcium bursts and prolongs the capacity of the myosin heads to crawl within each sarcomere involved, recruiting more force.

Figure 10.7 Ways to increase muscle contraction strength

However, if only the original muscle fibers synapsed by a single motor unit are used, force recruitment is limited. The second way to increase force is to recruit more synergistic motor units. Motor units whose fibers pull in the same direction are called synergistic motor units. There are two ways that these can be activated, and usually they are activated in sequence. First, muscle fibers within the same muscle mass are recruited to increase the force that mass engages (e.g., the biceps engage more and more muscle fibers the heavier the barbell while bicep curls). After all the muscle fibers within a single muscle mass are recruited, then synergistic muscle masses are engaged. We may also engage alternative muscle masses that do not pull in exactly the same direction because of where tendons attach for different defined muscles, but still contribute some force in our desired direction.

You can use both of these force generation mechanisms in your daily motor movements. Typically, your nervous system activates motor units in a sequential order to support much stronger contractions. The first motor units to be activated are smaller, with fewer connected muscle fibers, and the later recruited fibers will be larger and connected to more muscle fibers (explained later). On top of this sequential activation of motor units, your nervous system can increase the firing frequency of the motor neurons controlling the motor units, causing renewed action potentials and therefore more calcium bursts, thus prolonging the contraction for each fiber. By analogy, force generation through more action potentials would be like a tug-of-war team pulling harder and harder, while the second method of recruiting more motor units would be like adding more larger and stronger members to the team.