Chapter 7 - Neurons 2 - Intermediate Human Physiology Instructor: Meng Wang PDF

Preview

Summary

Intermediate Human Physiology
Instructor: Meng Wang...

Description

7.1 NEURONS AND SUPPORTING CELLS The nervous system is divided into the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which includes the cranial nerves arising from the brain and the spinal nerves arising from the spinal cord. The nervous system is composed of only two principal types of cells: Neurons: • • •

•

the basic structural and functional units of the nervous system; specialized to respond to physical and chemical stimuli, conduct electrochemical impulses, and release chemical regulators; enable the perception of sensory stimuli, learning, memory, and the control of muscles and glands. Most cannot divide by mitosis, although many can regenerate a severed portion or sprout small new branches under certain conditions.

Supporting cells: • •

•

aid the functions of neurons and are about five times more abundant than neurons. collectively called neuroglia, or simply glial cells are able to divide by mitosis. This helps to explain why brain tumors in adults are usually composed of glial cells rather than of neurons.

Neurons Although neurons vary considerably in size and shape, they generally have three principal regions: (1) a cell body, (2rites, and (3) an axon. Dendrites and axons can be referred to generically as processes, or extensions from the cell body. The cell body is the enlarged portion of the neuron that contains the nucleus. It is the “nutritional center” of the neuron where macromolecules are produced. The cell body and larger dendrites (but not axons) contain Nissl bodies, which are seen as dark-staining granules under the microscope. Nissl bodies are composed of large stacks of rough endoplasmic reticulum that are needed for the synthesis of membrane proteins. The cell bodies within the CNS are frequently clustered into groups called nuclei. Cell bodies in the PNS usually occur in clusters called ganglia Dendrites are thin, branched processes that extend from the cytoplasm of the cell body. Dendrites provide a receptive area that transmits graded electrochemical impulses to the cell body. The axon is a longer process that conducts impulses, called action potentials, away from the cell body. The origin of the axon near the cell body is an expanded region called the axon hillock. Toward their ends, axons can produce up to 200 or more branches called axon collaterals, and each of these can divide to synapse with many other neurons.

Classification of Neurons and Nerves The functional classification is based on the direction in which they conduct impulses • •

•

Sensory, or afferent, neurons conduct impulses from sensory receptors into the CNS. Motor, or efferent, neurons conduct impulses out of the CNS to effector organs (muscles and glands). o Somatic motor neurons are responsible for both reflex and voluntary control of skeletal muscles. o Autonomic motor neurons innervate (send axons to) the involuntary effectors— smooth muscle, cardiac muscle, and glands. ▪ Sympathetic – emergency situations ▪ Parasympathetic – normal functions ▪ Autonomic motor neurons, together with their central control centers, constitute the autonomic nervous system. Association neurons, or interneurons, are located entirely within the CNS and serve the associative, or integrative, functions of the nervous system.

The structural classification of neurons is based on the number of processes that extend from the cell body •

• •

Pseudounipolar neurons have a single short process that branches like a T to form a pair of longer processes. o Sensory neurons are pseudounipolar—one of the branched processes receives sensory stimuli and produces nerve impulses; the other delivers these impulses to synapses within the brain or spinal cord. Bipolar neurons have two processes, one at either end; this type is found in the retina of the eye. Multipolar neurons, the most common type, have several dendrites and one axon extending from the cell body; motor neurons are good examples of this type.

A nerve is a bundle of axons located outside the CNS. Most nerves are composed of both motor and sensory fibers and are thus called mixed nerves. Some of the cranial nerves, however, contain sensory fibers only. These are the nerves that serve the special senses of sight, hearing, taste, and smell. A bundle of axons in the CNS is called a tract.

Neuroglial Cells Unlike other organs that are “packaged” in connective tissue derived from mesoderm (the middle layer of embryonic tissue), most of the supporting cells of the nervous system are derived from the same embryonic tissue layer (ectoderm) that produces neurons. The term neuroglia (or glia) traditionally refers to the supporting cells of the CNS, but in current usage the supporting cells of the PNS are often also called glial cells. There are two types of neuroglial cells in the PNS: 1. Schwann cells (neurolemmocytes), which form myelin sheaths around peripheral axons; and 2. satellite cells, or ganglionic gliocytes, which support neuron cell bodies within the ganglia of the PNS. There are four types of neuroglial cells in the CNS: 1. oligodendrocytes, which form myelin sheaths around axons of the CNS; 2. microglia, which migrate through the CNS and phagocytose foreign and degenerated material;

o Infection, trauma, or any altered state can lead to microglial activation, in which the cells become amoeboid in shape and are transformed into phagocytic, motile cells. 3. astrocytes, which help to regulate the external environment of neurons in the CNS; and 4. ependymal cells, which are epithelial cells that line the ventricles (cavities) of the brain and the central canal of the spinal cord.

Neurilemma and Myelin Sheath All axons in the PNS (myelinated and unmyelinated) are surrounded by a continuous living sheath of Schwann cells, known as the neurilemma, or sheath of Schwann. The axons of the CNS, by contrast, lack a neurilemma (Schwann cells are found only in the PNS). Some axons in the PNS and CNS are surrounded by a myelin sheath. In the PNS, this insulating covering is formed by successive wrappings of the cell membrane of Schwann cells; in the CNS, it is formed by oligodendrocytes. Those axons smaller than 2 micrometers (2 mm) in diameter are usually unmyelinated (have no myelin sheath), whereas those that are larger are likely to be myelinated. Myelinated axons con- duct impulses more rapidly than those that are unmyelinated.

Myelin Sheath in PNS In the process of myelin formation in the PNS, Schwann cells attach to and roll around the axon; the Schwann cell wrappings are made in the same spot, so that each wrapping overlaps the previous layers. The cytoplasm, meanwhile, is forced into the outer region of the Schwann cell. Each Schwann cell wraps only about a millimeter of axon, leaving gaps of exposed axon between the adjacent Schwann cells. These gaps in the myelin sheath are known as the nodes of Ranvier. The successive wrappings of Schwann cell membrane provide insulation around the axon, leaving only the nodes of Ranvier exposed to produce nerve impulses. The Schwann cells remain alive as their cytoplasm is forced to the outside of the myelin sheath. As a result, myelinated axons of the PNS are surrounded by a living sheath of Schwann cells, or neurilemma. Unmyelinated axons are also surrounded by a neurilemma, but they differ from myelinated axons in that they lack the multiple wrappings of Schwann cell plasma membrane that compose the myelin sheath.

Myelin Sheath in CNS The myelin sheaths of the CNS are formed by oligodendrocytes. Unlike a Schwann cell, which forms a myelin sheath around only one axon, each oligodendrocyte has extensions, like the tentacles of an octopus, that form myelin sheaths around several axons. The myelin sheaths around axons of the CNS give this tissue a white color; areas of the CNS that contain a high concentration of axons thus form the white matter. The gray matter of the CNS is composed of high concentrations of cell bodies and dendrites, which lack myelin sheaths. Demyelinating diseases are those in which the myelin sheaths are specifically attacked. Because Schwann cells form the myelin in the PNS, whereas oligodendrocytes form the myelin of the CNS, the immune system attacks one or the other type of myelin: Guillain-Barre syndrome: the T cells of the immune system attack myelin sheaths of the PNS. This produces rapid onset of symptoms that include muscle weakness (which can dangerously affect the muscles of breathing) due to dysfunction of somatic motor axons, and cardiac and blood pressure problems due to dysfunction of autonomic axons. Multiple sclerosis (MS) is produced by autoimmune attack mediated by T cells on the myelin sheaths in the CNS. This leads to areas of hardening, or scleroses, followed by axonal degeneration. It is a chronic remitting and relapsing disease with highly variable symptoms, including sensory impairments, motor dysfunction and spasticity, bladder and intestinal problems, fatigue, and others.

Regeneration of a Cut Axon When an axon in a peripheral nerve is cut, the distal portion of the axon that was severed from the cell body degenerates and is phagocytosed by Schwann cells. The Schwann cells, surrounded by the basement membrane, then form a regeneration tube as the part of the axon that is connected to the cell body begins to grow and exhibit amoeboid movement. The Schwann cells of the regeneration tube are believed to secrete chemicals that attract the growing axon tip, and the regeneration tube helps guide the regenerating axon to its proper destination. Even a severed major nerve may be surgically reconnected—and the function of the nerve largely reestablished—if the surgery is performed before tissue death occurs. After spinal cord injury, some neurons die as a direct result of the trauma. However, other neurons and oligodendrocytes in the region die later because they produce “death receptors” that promote apoptosis. Injury in the CNS stimulates growth of axon collaterals, but central axons have a much more limited ability to regenerate than peripheral axons. Regeneration of CNS axons is prevented, in part, by inhibitory proteins in the membranes of the myelin sheaths. Also, regeneration of CNS axons is prevented by a glial scar that eventually forms from astrocytes. This glial scar physically blocks axon regeneration and induces the production of inhibitory proteins. Surprisingly, Schwann cells in the PNS also produce myelin proteins that can inhibit axon regeneration. However, after axon injury in the PNS, the fragments of old myelin are rapidly removed (through phagocytosis) by Schwann cells and macrophages. Also, quickly after injury the Schwann cells stop producing the inhibitory proteins. The rapid changes in Schwann cell function following injury create an environment conducive to axon regeneration in the PNS.

7.2 ELECTRICAL ACTIVITY IN AXONS All cells in the body maintain a potential difference (voltage) across the membrane, or resting membrane potential (rmp), in which the inside of the cell is negatively charged in comparison to the outside of the cell. The membrane traps large, negatively charged organic molecules within the cell and permits only limited diffusion of positively charged inorganic ions. These properties result in an unequal distribution of these ions across the membrane. The action of the Na+/K+ pumps also helps to maintain a potential difference because they pump out 3 sodium ions (Na +) for every 2 potassium ions (K+) that they transport into the cell. Partly as a result of these pumps, Na+ is more highly concentrated in the extracellular fluid than inside the cell, whereas K1 is more highly concentrated within the cell. Although all cells have a membrane potential, only a few types of cells have been shown to alter their membrane potential in response to stimulation. Such alterations in membrane potential are achieved by varying the membrane permeability to specific ions in response to stimulation. A central aspect of the physiology of neurons and muscle cells is their ability to produce and conduct these changes in membrane potential. Such an ability is termed excitability or irritability. An increase in membrane permeability to a specific ion results in the diffusion of that ion down its electrochemical gradient (concentration and electrical gradients, considered together), either into or out of the cell. These ion currents occur only across limited patches of membrane where specific ion channels are located.

At rest, a cell is considered polarized when the inside is more negative than the outside. If appropriate stimulation causes positive charges to flow into the cell, the membrane potential inside the cell increased (the line will deflect upward). This change is called depolarization (or hypopolarization) A return to the resting membrane potential is known as repolarization. If stimulation causes the inside of the cell to become more negative than the resting membrane potential, it is called hyperpolarization (the line on the oscilloscope will deflect downward). Hyperpolarization can be caused either by positive charges leaving the cell or by negative charges entering the cell. Depolarization of a dendrite or cell body is excitatory, whereas hyperpolarization is inhibitory, in terms of their effects on the production of nerve impulses.

Ion Gating in Axons Ions such as Na+, K+, and others pass through ion channels in the plasma membrane that are said to be gated channels. The “gates” are part of the proteins that compose the channels, and can open or close the ion channels in response to particular stimuli. When ion channels are closed, the plasma membrane is less permeable, and when the channels are open, the membrane is more permeable to an ion. The ion channels for Na+ and K+ are specific for each ion. There are two types of channels for K+. One type is gated, and the gates are closed at the resting membrane potential. The other type is not gated; these K+ channels are thus always open and are often called leakage channels. Channels for Na+, by contrast, are all gated and the gates are closed at the resting membrane potential. However, the gates of closed Na+ channels appear to flicker open (and quickly close) occasionally, allowing some Na + to leak into the resting cell. As a result of these ion channel characteristics, the neuron at the resting membrane potential is much more permeable to K+ than to Na+, but some Na+ does enter the cell. Because of the slight inward movement of Na+, the resting membrane potential is a little less negative than the equilibrium potential for K+. Depolarization to a threshold level causes the Na+ channels to open (at -55mV) Now, for an instant, the plasma membrane is freely permeable to Na+. Because the inside of the cell is negatively charged relative to the outside, and the concentration of Na+ is lower inside of the cell, the electrochemical gradient (the combined electrical and concentration gradients) for Na+ causes Na+ to rush into the cell. This causes the membrane potential to move rapidly toward the sodium equilibrium potential. The number of Na+ ions that actually rush in is relatively small compared to the total, so the extracellular Na+ concentration is not measurably changed. However, the increased Na+ within that tiny region of axon membrane greatly affects the membrane potential. A fraction of a second after the Na+ channels open, they close due to an inactivation process (at +30mV). Just before they do, the depolarization stimulus causes the gated K+ channels to open (at around +30mV). This makes the membrane more permeable to K+ than it is at rest, and K+ diffuses down its electrochemical gradient out of the cell. This causes the membrane potential to move toward the potassium equilibrium potential (repolarize). The K+ gates will then close and the permeability properties of the membrane will return to what they were at rest. Repolarization actually overshoots resting potential and gets down to -85mV, but it is quickly reestablished by the pump.

Because opening of the gated Na+ and K+ channels is stimulated by depolarization, these ion channels in the axon membrane are said to be voltage-regulated, or voltage-gated, channels. The channel gates are closed at the resting membrane potential of 270 mV and open in response to depolarization of the membrane to a threshold value.

Action Potentials When the axon membrane has been depolarized to a threshold level the Na+ gates open and the membrane becomes permeable to Na+. This permits Na+ to enter the axon by diffusion, which further depolarizes the membrane (makes the inside less negative, or more positive). The gates for the Na + channels of the axon membrane are voltage regulated, and so this additional depolarization opens more Na+ channels and makes the membrane even more permeable to Na+. As a result, more Na+ can enter the cell and induce a depolarization that opens even more voltage-regulated Na+ gates. A positive feedback loop is thus created, causing the rate of Na + entry and depolarization to accelerate in an explosive fashion. The explosive increase in Na+ permeability results in a rapid reversal of the membrane potential in that region from 270 mV to 130 mV. At that point the channels for Na+ become inactivated causing a rapid decrease in Na+ permeability. This is why, at the top of the action potential, the voltage does not quite reach the 166 mV equilibrium potential for Na+. Also at this time, as a result of a time-delayed effect of the depolarization, voltage-gated K+ channels open and K+ diffuses rapidly out of the cell. Because K+ is positively charged, the diffusion of K+ out of the cell makes the inside of the cell less positive, or more negative, and acts to restore the original resting membrane potential of 270 mV. This process is called repolarization and represents the completion of a negative feedback loop. These changes in Na+ and K+ diffusion and the resulting changes in the membrane potential they produce constitute an event called the action potential, or nerve impulse. The peak action potential depolarization is less than the Na1 equilibrium potential (166 mV), due to inactivation of the Na1 channels. The Na+/K+ pumps are constantly working in the plasma membrane. This movement is sufficient to cause changes in the membrane potential during an action potential but does not significantly affect the concentrations of these ions. Thus, active transport is still required to move Na1 out of the axon and to move K1 back into the axon after an action potential. A neuron poisoned with cyanide so that it cannot produce ATP can still produce action potentials for a period of time. After a while, however, the lack of ATP for active transport will result in a decline in the concentration gradients, and therefore in the ability of the axon to produce action potentials. This shows that the Na+/K+ pumps are not directly involved; rather, they are required to maintain the concentration gradients needed for the diffusion of Na+ and K+ during action potentials.

All-or-None Law Once a region of axon membrane has been depolarized to a threshold value, the positive feedback effect of depolarization on Na+ permeability and of Na+ permeability on depolarization causes the membrane potential to shoot toward about 130 mV. It does not normally become more positive than 130 mV because the Na+ channels quickly close and the K1 channels open. The length of time that the Na+ and K+ channels stay open is independent of the strength of the depolarization stimulus. The amplitude (size) of action potentials is therefore all- or-none. When depolarization is below a threshold value, the voltage-regulated gates are closed; when depolarization reaches threshold, a maximum potential change (the action potential) is produced. Inactivation occurs automatically and lasts until the membrane has repolarized.

Coding for Stimulus Intensity Because action potentials are all-or-none events, a stronger stimulus cannot produce an action potential of greater amplitude. The code f...