Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Cells and Molecules at Work
Nerves in Action

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Fig. 36.1.

NERVES are long, specialized structures that coordinate bodily Functions and mediate responses to various stimuli. Nerve Cells, also known as Neurons, are found in many organisms. Each nerve Cell consists of a cell body and a long extension called an axon. The vertebrate Nervous system is divided into the Central Nervous System (CNS) and the Peripheral Nervous System (PNS). The CNS integrates a vast number of nerves and relays information between them. Its two main components are the Brain and the Spinal Cord. The PNS consists of two parts: afferent nerves, whose axons transmit signals from external stimuli receptors to the CNS, and efferent nerves, whose axons carry signals from the CNS to target Tissues and Organs. Organs and tissues controlled by nerves are referred to as innervated. The simplest mechanism of nervous regulation is the monosynaptic reflex.

A MONOSYNAPTIC REFLEX ARC is a neural pathway formed by two neurons. The first neuron functions as a receptor element that receives a stimulus from the stretch-sensitive region of a Muscle spindle: when a muscle is stretched, mechanical movement generates a chemical signal, which in turn induces an electrical impulse transmitted along the axon of this primary sensory neuron (the afferent pathway of the reflex arc). At the axon terminal, located within the spinal cord or brain, There is a specialized junction called a synapse with the second neuron, a motor neuron. The synapse consists of a presynaptic element, which is the nerve terminal of the afferent fiber, and a postsynaptic element located on The Cell body of the motor neuron. These two elements are separated by the synaptic cleft. Via a specialized chemical messenger known as a neurotransmitter, the impulse is transmitted across the synaptic cleft and then propagates along the motor neuron's axon (the efferent pathway of the reflex arc) to the effector ending on the muscle. Transmission of the impulse to the muscle via the subsequent synapse triggers calcium release and Muscle contraction (Chapter 37). Thus, stretching of the muscle spindle induces a reflex contractile response in the muscle.

The presynaptic element is a specialized Membrane Structure at the nerve terminal. The nerve ending contains vesicles filled with neurotransmitter. An arriving Action Potential triggers the fusion of these vesicles with the presynaptic membrane, releasing the neurotransmitter into the synaptic cleft.

Neurotransmitters are small charged molecules that, upon release from the presynaptic membrane, bind to receptors on the postsynaptic membrane. Examples include glutamate [+NH₃-CH(CH₂CH₂COO)—COOH], which is found primarily in CNS synapses, and acetylcholine [CH₃—COO—CH₂—CH₂— +N(CH₃)₃], which is used predominantly in the PNS.

The postsynaptic element is formed by the membrane of nerve cell dendrites (in CNS synapses) or the sensitive membrane of target tissue cells innervated by a motor neuron (in PNS synapses). The membrane of the motor end plate, densely packed with neurotransmitter acetylcholine receptors, serves as the postsynaptic element of the peripheral synapse at the terminus of a monosynaptic reflex arc.

Axons are long fibers that transmit electrical signals from one nerve terminal to the next. Each nerve cell has only a single axon. Axon length varies across a wide range; axons of many motor neurons located in the CNS reach the most distant PARTS OF THE Muscles they innervate. When axons are covered by an insulating sheath called myelin (see below), they are referred to as myelinated. The diameter of axons in myelinated nerves falls within a relatively narrow range of 1—20 µm, whereas unmyelinated axons may range from 0.1 to 500 µm in diameter. Due to the insulating properties of myelin, impulse propagation velocity is higher in myelinated nerves than in unmyelinated ones. In mammals, for instance, a myelinated nerve with a diameter of 20 µm achieves a conduction velocity of up to 120 m/s, whereas for an unmyelinated nerve with a diameter of 1 µm it may be as low as 2 m/s. The absence of myelin can be compensated for by an increase in axon diameter; thus, the squid axon (which is unmyelinated) has a diameter of 500—1000 µm and conducts impulses at a velocity of about 20 m/s.

Myelinated axons are surrounded by specialized glial cells that produce a lipoprotein membrane known as myelin. The membrane of these cells wraps around the axon, forming a multi-layered sheath that functions as an insulator. In neurons belonging to the CNS, the myelin-forming cells are oligodendrocytes, whereas in PNS neurons they are Schwann cells. The neuron axon shown in Fig. 36.1 is part of a peripheral myelinated nerve. The myelin sheath is constructed of a lipid membrane consisting of lecithin-Cholesterol and sphingomyelin-cholesterol (chapters 32, 33), bound primarily to two Proteins: a lipoprotein and a basic protein. The basic protein is located on the outer surface of the membrane (chapter 34), enabling it to stabilize successive membrane layers in the myelin "scroll": its positively charged C-terminal domain, projecting into the intermembrane space, forms ionic bonds with the negatively charged Lipids of the adjacent membrane layer. In this manner, each membrane layer is firmly held in contact with neighboring layers.

Nerve Impulse propagation occurs as a wave of depolarization traveling down the axon from the cell body to the nerve terminal. At any given point on a resting axon membrane—before the depolarization wave reaches it—there is a transmembrane potential (ф) of approximately —70 mV (with a negative charge excess on the inside). This potential is established by the unequal distribution of Na⁺ and K⁺ between the intra- and extracellular spaces (chapter 38) and the selective permeability of the membrane. When an impulse arrives at the point in question, of sufficient magnitude to induce A change in ф exceeding the threshold value (about 10 mV), a series of sodium channels located in the axonal Plasma Membrane open. This initiates a cycle of changes in ф known as the action potential. In myelinated axons, The Plasma Membrane contacts the Na+-containing extracellular fluid only at specific points—the nodes of Ranvier—and membrane depolarization occurs exclusively at these nodes.

An action potential is generated when an impulse reaches a node and Na⁺ enters the axon via transmembrane potential-sensitive channels. The Membrane Potential rapidly shifts (in less than 1 ms) from —70 mV to 0 mV (complete depolarization) and further to approximately +20 mV (with a positive charge excess on the inside). This phase of the action potential corresponds to the brown section of the graph in Fig. 36.1. Because Na⁺ ions carry positive charges into the cell, the initial effect produced by the stimulating potential is amplified, causing even more sodium channels to open. When all channels at the node are

open, the value of ф there reaches its maximum. Because the axon is insulated by myelin, electric current cannot spread effectively along the axon via the membrane; instead, its propagation to the next node occurs primarily through the axonal Cytoplasm. Repolarization results from the efflux of K⁺ ions out of the axon, which takes somewhat longer (2—3 ms) than the influx of Na⁺ (this phase corresponds to the dotted portion of the graph in Fig. 36.1). Until repolarization is complete, the node cannot be re-excited (the refractory period), and by the time the node is once again responsive, the impulse has already traveled too far down the axon to reopen the sodium channels at the site in question. For this reason, impulses propagate along the axon in only one direction. The final stage of repolarization begins after The Active Transport ATPases of the axonal membrane restore the normal concentration ratios of Na⁺ and K⁺ (this stage corresponds to the hatched area of the graph). It should be emphasized that electrical changes across the axonal membrane are driven by very minor shifts in intracellular and extracellular Na⁺ and K⁺ concentrations. The critical parameter is The rate of ion movement across the membrane, which is indicated in Fig. 36.1 near the arrows showing the direction of ion transport. The duration of an action potential may be less than 1/5 s. In humans, for example, the knee-jerk reflex response takes about 35 ms. Stimuli arriving at sensory neurons can vary in strength. Information regarding the intensity of the input signal is encoded as the frequency of action potential generation. Thus, intense muscle contraction is driven by a high frequency of action potentials, and vice versa.