NERVOUS TISSUE Organization of the Nervous System Histology of Nervous Tissue 1. Neuroglia - the "glue" that holds the nervous system together - functions for support and protection - five basic types (1) Astrocytes - star shaped - help form the blood-brain barrier - two types - protoplasmic astrocytes - gray matter of the CNS - fibrous astrocytes - white matter of the CNS (2) Oligodendrocytes - make up the myelin sheath in CNS (3) Microglia - engulf and destroy microbes (4) Ependyma - epithelial lining of the ventricles of the brain - aid in the circulation of CSF (5) Schwann cells - make up the myelin sheath in the PNS. 41 The Schwann cell is found in the peripheral nervous system. The image below shows how it wraps itself around the axon to form a myelin sheath. Neurons - conduct nerve impulse from one part of the body to another - types of synapses - neuromuscular junction - synapse between a motor neuron and a muscle - neuroglandular junction - synapse between a neuron and a gland Structure of neurons - have a cell body with: - a well defined nucleus - nucleolus - Cytoplasmic processes - Dendrites - conduct nerve impulses toward the cell body - highly branched - Axons - conduct nerve impulses away from the cell body - originate from region of cell body called the axon hillock - contain cytoplasm called axoplasm - the cell membrane of the axon is called the axolemma - may have side branches called axon colaterals - the axon branches into telodendria (axon terminals) - each telodendria has a synaptic bulb on its end with neurotransmitter - nerve fiber - a process (axon or dendrite) extending from the cell body - nerve = many fibers bundled together with connective tissue in the PNS - tract = fibers bundled together in the CNS 42 Myelination of Nerve Fibers (see the Schwann cell image above) - most nerve fibers outside the CNS are myelinated - myelination accomplished by Schwann cells - Schwann cells wrap themselves around the nerve fiber such that the innermost portion of the Schwann cell is devoid of cytoplasm and just consists of the cell membrane. This portion is called the Myelin Sheath. - the outer portion of the Schwann cell receives all of the cytoplasm and nucleus and is surrounded by cell membrane called the neurolemma - the Schwann cells are wrapped around nerve fibers in such a manner that gaps are left between the Schwann cells where axolemma is exposed - these gaps are called the Nodes of Ranvier Classification of Neurons 1. Multipolar Neurons - several dendrites and one axon - make up most neurons in the brain and spinal cord and motor neurons in the PNS 2. Bipolar Neurons - one dendrite and one axon - found in retina, inner ear, olfactory area. 3. Unipolar Neurons - only one process extending from the cell body - general somatic sensory neurons 43 44 Functional Classification of Neurons 1. Motor Neurons - convey impulses from the CNS to effectors (muscles and glands) so said to be Efferent Neurons. 2. Sensory Neurons - convey impulses from receptors to the CNS and said to be Afferent 3. Association Neurons (connecting, internuncial, interneuron) - connect sensory neurons to motor neurons in the CNS Saltatory Conduction - myelin does not conduct nerve impulses - however, the myelin is interrupted periodically be nodes of Ranvier - thus the impulse jumps from node to node (like a rabbit) Speed of Nerve Impulse - is independent of stimulus strength - speed is dependent on: - temperature - fiber diameter - myelination 45 Chemical Composition of extracellular fluid and intracellular fluid Intracellular fluid = fluid inside the cell - high levels of K+, Mg++, Phosphates, Amino acids, proteins - low levels of Na+, Cl-, HCO3-, glucose Extracellular fluid = fluid around the cell and blood plasma - concentrations the opposite of intracellular fluid Transport Proteins - lipid bilayer is a barrier for the movement of most water soluble substances between intra and extracellular fluids - integral proteins offer a pathway through the cell membrane and can be referred to as transport proteins of which there are two types 1. Channel Proteins have a watery space all the way through the cell membrane and allow the passage of ions and other molecules 2. Carrier Proteins bind with molecules and move them through the membrane \ 46 Protein Channels and Gating - protein channels have two characteristics 1. they are often selectively permeable to certain substances. 2. Many of the channels can be opened or closed by gates. Selective Permeability - Some channels like sodium channels have the inner surface of the channel strongly negatively charged and have a diameter of the right size for sodium to pass. - the combination of channel diameter and negative charge leads to the passage of sodium because the ratio of pulling force to ionic diameter is far greater for sodium than any other ions. - as you can see in the diagram above, the Na+ ion cannot pass through the channel protein when the gate is closed, but it passed through readily when the gate is opened. Membrane Potentials and Action Potentials - electrical potentials exist across the membranes of essentially all cells of the body - chemical gradients also exist across the membrane due to differences in concentrations of sodium and potassium. - some cells (like muscle and nerve cells) are capable of using this potential to selfgenerate electrochemical impulses at their membranes, and to transmit these impulses along the cell membrane in all directions. Cells that can do this are said to be excitable. 47 Basics of Membrane Potentials - the intracellular and extracellular fluids contain almost equal concentrations of positive and negative ions - a minute excess of negative ions accumulates on the inside of the membrane - an equally minute concentration of positive ions accumulates on the outside of the membrane - in effect there is now a membrane potential has been established between the inside and the outside of the cell. Membrane Potentials caused by Active Transport - the cell membrane contains a transport protein called a sodium/potassium pump, which pumps three (3) sodium ions out of the cell for every two potassium ions it pumps in - establishing a higher concentration of sodium on the outside of the cell membrane than potassium on the inside of the cell membrane leading to a net negativity of about 90mv. on the inside Gating of Protein Channels - gating provides a means for controlling the permeability of the channels - gates are extensions of the transport protein which can close over the opening of the channel - the opening and closing of the gates are controlled in two ways 1. Voltage Gating - the molecular conformation of the gate responds to the electrical potential across the cell membrane - in other words - when the inside of the channel loses its negative charge the gate opens. 2. Ligand Gating - the gate opens when another molecule binds with the transport protein causing a conformational change - this will be important later when we look at neurotransmitters like acetylcholine. The Sodium/Potassium Pump - transports three (3) sodium ions out of the cells to the exterior and at the same time pumps two (2) potassium ions from the outside to the inside of the cell.. - present in all the cells of the body - maintains sodium and potassium concentration differences across the cell membrane - establishes a negative electrical potential inside the cell. - pump has three important functions: 1. It has three receptor sites for binding with sodium on the outside of the protein. 2. It has two receptor sites for binding with potassium on the inside of the protein. 3. The inside portion of this protein adjacent to or near the sodium binding sites has ATPase activity (see figure on the next page) 48 How the pump works - when three sodium ions bind on the inside of the carrier protein and two potassium ions bind on the outside, the ATPase is activated. The molecule of ATP is cleaved, splitting it into ADP + P and liberating a high energy phosphate bond for energy. This energy causes the carrier protein to change shape pushing the sodium ions to the outside of the cell membrane and the potassium ions to the inside of the cell membrane. The fact that the sodium/potassium pump moves three sodium ions out of the cell for every two potassium ions it moves into the cell means that there is a net of one positive ion moved from the interior to the exterior for each revolution of the sodium/potassium pump. This establishes a net positive charge on the outside of the cell membrane relative to the inside the cell membrane of about -90mv. Therefore the sodium/potassium pump is said to be electrogenic because it creates an electrical potential across the cell membrane. The Nerve Action Potential - rapid changes in the membrane potential - each action potential begins with a sudden change from the normal resting membrane potential (of positive on the outside of the membrane relative to the inside) to a depolarization stage (where the outside of the membrane is negative relative to the inside) and then ends with an equally rapid repolarization stage (where the outside of the membrane is once again positive relative to the inside of the membrane). - the successive stages of the action potential are then: 1. Resting stage 2. Depolarization stage. 3. Repolarization. 1. Resting stage the resting membrane potential is established 2. Depolarization stage - the membrane suddenly becomes permeable to sodium (a gated sodium channel undergoes a conformational change and opens) and large amounts of sodium rush into the cell (down the concentration gradient). - the resting membrane potential of -90mv is lost with the inside of the cell now becoming positive relative to the outside (due to the influx of all those sodium ions). 49 3. Repolarization stage - within a few 10,000ths of a second after the membrane becomes permeable to sodium the sodium channels close - the membrane suddenly becomes permeable to potassium (a gated potassium channel undergoes a conformational change and opens) and large amounts of potassium rapidly diffuse to the outside of the membrane (down the concentration gradient) reestablishing the outside of the membrane as positive relative to the inside. Note: both depolarization and repolarization are aided by voltage-gated channels. Initiation of the Action Potential - the membrane potential must move in the positive direction toward the zero level - a disturbance of the membrane causes the membrane potential to become more positive - the voltage-gated sodium channels are affected allowing sodium to enter the cell (down the concentration gradient) which causes the inside of the membrane to become more positive which opens more channels which causes the inside of the membrane to become more positive etc. - an action potential will not occur until the potential rises from -90mV up to -65mV How the action potential is propagated - an action potential elicited at any point on an excitable membrane usually excites nearby portions of the membrane resulting in movement (propagation) of the action potential. This occurs in the following manner: - a "local" current depolarizes adjacent areas - the sodium channels in these new areas immediately activate and the action potential spreads in all directions until the entire membrane has become depolarized - once an action potential has been elicited at any point on the membrane, the depolarization will spread over the entire membrane. This is called the ALL-OR-NONE principle 50 Propagation of Depolarization Propagation of Repolarization - the action potential normally lasts almost the same length of time at each point along a fiber - therefore, repolarization usually occurs first at the point of stimulus and then spreads progressively along the membrane, moving in the same direction that depolarization took. - as you can see above, the propagation of repolarization occurs in both directions along the nerve fiber Transmission at Synapse - allow integration of information - presynaptic neuron - releases neurotransmitter - postsynaptic neuron - receives neurotransmitter The Synapse - the axon of the presynaptic neuron has axon terminals that come close to the postsynaptic neuron but leave a small gap (called the synaptic cleft) - the components of this junction are: - synaptic end bulb containing sacs called: - synaptic vesicles that contain a chemical called a Neurotransmitter (Acetylcholine) - synaptic cleft - the gap between the end bulb and the muscle sarcolemma - subneural clefts that increase the surface area where acetylcholine can bind - acetylcholine receptors - integral proteins that function as ligand sodium gates 51 How a Synapse Occurs - a nerve impulse reaches the axon terminal - Ca++ channels open in the presynaptic membrane and Ca++ diffuses into the neuron - synaptic vesicles release acetylcholine into the synaptic cleft - ACh diffuses across the cleft and combines with receptor sites on the integral proteins - ACh-gated ion channels open (this is a ligand gate) allowing sodium to enter the muscle fiber, causing an action potential to occur Some of the most important Neurotransmitters are: 1. Achetylcholine - important in the following areas: - Motor cortex of the brain - Neuromuscular junctions - Preganglionic Neurons of the ANS - Postganglionic Neurons of the parasympathetic division of the ANS and some postganglionic Neurons of the sympathetic division of the ANS - Mostly excitatory effects - inhibitory at parasympathetic to heart 2. Norepinephrine - important in the following areas - brain stem and hypothalamus - postganglionic neurons of the sympathetic division of the ANS - can be excitatory or inhibitory 3. Dopamine - important in the following areas 52 - substantia nigra of the brain - inhibitory - involved in emotions and moods 4. Gamma-aminobutyric Acid (GABA) - important in the following areas - nerve terminals in spinal cord - cerebellum - basal ganglia - inhibitory - may play a role in pain reception 5. Enkephalins - important in the following areas - brain and spinal cord - excitatory to excite other systems that inhibit the transmission of pain 6. Serotonin - important in the following areas - dorsal horns of the spinal cord - hypothalamus of the brain - inhibitor for control of pain - involved in emotions, moods, and sleep 53