Motor end plates

At the myoneural junction, the axon divides into a handful of branchlets that groove the surface of the muscle fiber (Figure 10.2B). The underlying sarcolemma is thrown into junctional folds. The basement membrane of the muscle fiber traverses the synaptic cleft and lines the folds. The underlying sarcoplasm shows an accumulation of nuclei, mitochondria, and ribosomes known as a sole plate.

Each axonal branchlet forms an elongated terminal bouton containing thousands of synaptic vesicles loaded with acetylcholine (ACh). Synaptic transmission takes place at active zones facing the crests of the junctional folds (Figure 10.2C). Vesicular ACh is extruded at great speed by exocytosis into the synaptic cleft. The ACh diffuses through the basement membrane to bind with ACh receptors in the sarcolemma.

Activation of the receptors leads to depolarization of the sarcolemma. The depolarization is led into the interior of the muscle fiber by T tubules. The sarcoplasmic reticulum liberates Ca²⁺ ions that initiate contraction of the sarcomeres.

Acetylcholinesterase enzyme is concentrated in the basement membrane, and about 30% of released ACh is hydrolyzed without reaching the postsynaptic membrane. Following hydrolysis, the choline moiety is returned to the axoplasm.

Also in terminal boutons are some dense-cored vesicles containing one or more peptides (Figure 12.2C). Best known is calcitonin gene-related peptide, a potent vasodilator.

Details of the muscle fiber contraction process are in Box 10.2.

Box 10.2 Muscle fiber contraction

This flow diagram shows the sequential events taking place during the contraction of a single striated muscle fiber.

Motor units in the elderly

Progressive wasting of muscles seen in the elderly is mainly due to loss of motor neurons from the spinal cord and brainstem, often due in part to low-grade peripheral neuropathy arising from vascular disease and/or nutritional deficiency. Electromyographic records taken from contracting muscles show giant motor unit potentials during the seventh and eighth decades. The extra-large potentials result from takeover of vacated motor end plates of lost motor neurons by collateral sprouts from the axons of adjacent healthy motor units. Details of electromyography, and of clinical neuromuscular disorders, are in Chapter 12.

Neuromuscular spindles

Muscle spindles are up to 1 cm in length and vary in number from a dozen to several hundred in different muscles. They are abundant (a) in the antigravity muscles along the vertebral column, femur, and tibia; (b) in the muscles of the neck; and (c) in the intrinsic muscles of the hand. All these muscles are rich in slow, oxidative muscle fibers. Spindles are scarce where FG or FOG fibers predominate.

Muscle spindles contain up to a dozen intrafusal muscle fibers (Figure 10.3). (Ordinary muscle fibers are extrafusal in this context.) The larger intrafusal fibers emerge from the poles (ends) of the spindles and are anchored to connective tissue (perimysium). Smaller ones are anchored to the collagenous spindle capsule. At the spindle equator (middle), the sarcomeres are replaced almost entirely by nuclei, in the form of ‘bags’ (in wide fibers) or ‘chains’ (in slender fibers).

Figure 10.3 Neuromuscular spindle (simplified). Large arrows indicate passive stretch of the annulospiral endings produced by lengthening of the relaxed muscle as a whole. Medium arrows indicate active stretch of annulospiral endings produced by activity of fusimotor nerve fibers. Active stretch more than compensates for the unloading effect of simultaneous extrafusal muscle fiber contraction. Small arrows indicate directions of impulse conduction to and from the spindle when the parent muscle is in use.

Passive stretch

Passive stretch of muscle spindles occurs when an entire muscle belly is passively lengthened. For example, in eliciting a tendon reflex such as the knee jerk, the spindles in the belly of the quadriceps muscle are passively stretched when the tendon is struck. The type Ia and type II fibers discharge to the spinal cord, where they synapse on the dendrites of α motor neurons (Figure 10.4). (α Motor neurons are so called because they give rise to axons of Aα diameter.) The response to the positive feedback from spindles is a twitch of contraction in the extrafusal muscle fibers of quadriceps. The spindles, because they lie in parallel with the extrafusal muscle, are passively shortened; they are described as being unloaded.

Figure 10.4 Patellar reflex, including reciprocal inhibition. Arrows indicate nerve impulses. (1) A tap to the patellar ligament stretches the spindles in quadriceps femoris. (2) Spindles discharge excitatory impulses to the spinal cord. (3) Alpha motor neurons respond by eliciting a twitch in quadriceps, with extension of the knee. (4 and 5) Ia inhibitory internuncials respond by suppressing any activity in the hamstrings.

Tendon reflexes are monosynaptic reflexes. They have a latency (stimulus–response interval) of about 15–25 ms.

In addition to exciting homonymous motor neurons (i.e. motor neurons supplying the same muscles), the spindle afferents inhibit the α motor neurons supplying the antagonist muscles, through the medium of inhibitory internuncial (interposed) neurons (Figure 10.4). This effect is called reciprocal inhibition. The inhibitory neurons involved are called Ia internuncials.

Active stretch

Active stretch is produced by the fusimotor neurons, which elicit contraction of the striated segments of the intrafusal muscle fibers. Because the connective tissue attachments are relatively fixed, the intrafusal fibers stretch the spindle equators by pulling them in the direction of the spindle poles (Figure 10.5). (This could be called a ‘Christmas cracker’ effect.)

Figure 10.5 Active stretch of a muscle spindle under isometric conditions. The term isometric means ‘same length’. Certainly, the extrafusal muscle fibers would remain isometric when pulling with both ends rigidly fixed. The muscle spindle also remains isometric, being anchored to the plate indirectly via connective tissue. But the striated elements of each intrafusal fiber do not remain isometric: they shorten because the spindle equator is elastic and yields to stress. The primary and secondary spindle afferents, applied to the equator, respond to the ‘active’ stretch produced by fusimotor activity by discharging afferent impulses to the CNS, with consequent reinforcement of extrafusal contraction via the gamma loop.

During all voluntary movements, Aα and Aγ motor neurons are coactivated by the corticospinal (pyramidal) tract. As a result, the spindles are not unloaded by extrafusal muscle contraction. Through ascending connections, the spindle afferents on both sides of the relevant joints are able to keep the brain informed about contractions and relaxations during any given movement.

Tendon endings

Golgi tendon organs are found at muscle–tendon junctions (Figure 10.6). A single Ib caliber nerve fiber forms elaborate sprays that intertwine with tendon fiber bundles enclosed within a connective tissue capsule.

Figure 10.6 Golgi tendon organ.

A dozen or more muscle fibers insert into the intracapsular tendon fibers, which are in series with the muscle fibers. The bulbous nerve endings are activated by the tension that develops during muscle contraction. Because the rate of impulse discharge along the parent fiber is related to the applied tension, tendon endings signal the force of muscle contraction.

The Ib afferents exert negative feedback on to the homonymous motor neurons, in contrast to the positive feedback exerted by muscle spindle afferents. The effect is called autogenetic inhibition, and the reflex arc is disynaptic because of the interpolation of an inhibitory neuron (Figure 10.7). If need be, there follows reciprocal excitation of motor neurons supplying antagonist muscles.

Figure 10.7 Reflex effects of Golgi tendon organ (GTO) stimulation. (1) Agonist contraction excites GTO afferent, which (2) excites inhibitory internuncial synapsing on (4) homonymous motor neuron, and (3) excites excitatory internuncial synapsing on (4) motor neuron supplying antagonist.

An important function of tendon organ afferents is to dampen (restrict) the inherent tendency of moving limb segments to oscillate (sway to and fro). Dampening introduces an element known to physiologists as joint stiffness. Paradoxically, when 1b afferents are allowed too much freedom, as in Parkinson’s disease (Ch. 28), they reinforce the inherent tendency to oscillate, and contribute to the characteristic resting tremor that is most obvious in the forearm (pronation–supination) and in the fingers (‘pill-rolling’ of the thumb pad by adjacent fingers).

Free nerve endings

Muscles are rich in freely ending nerve fibers, distributed to the intramuscular connective tissue and investing fascial envelopes. They are responsible for pain sensation caused by direct injury or by accumulation of metabolites including lactic acid. See also Clinical Panel 10.1.