Lecture 2/Nervous System PDF

‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ Lecture 2/Nervous system Impu...

‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ Lecture 2/Nervous system Impulses formation: Impulse: Electrical (Charge exchange on each side of the axon membrane), Physical (Change in membrane permeability) and chemical changes (energy production and release).It is simply the movement of action potentials along a nerve cell. All cells in the body maintain differences (Voltage) across the membrane , or (resting membrane potential) , in which the inside of the cell is negatively charged in comparison to the outside of the cell , in neurons it is equal to -70 mv , in muscle it is equal to – 85 mv. In resting potential , the cell membrane is High permeability to K+ , Less permeability to Cl- and Na+ and the presence of organic big negatively charged molecules (Proteins) inside the axon, makes the inside negatively charged and the outside positively charged. After stimulation, the membrane become in action potential and said to be (depolarized) , the membrane become High permeability to Na+ , Less permeability to K+. Action potential are localized (only affect a small area of nerve cell membrane).So, when one occurs, only a small area of membrane depolarizes. As a result, for a split second, areas of membrane adjacent to each other has opposite charges (The depolarized membrane is negative on the outside and positive on the inside). An electrical circuit or mini-circuit develops between these oppositely charged areas). The mini- circuit stimulates the adjacent area and, therefore, an action potential occurs. This process repeats itself and action potentials move down the nerve cell membrane. Action potential is a very rapid change in membrane potential that occurs when a nerve cell membrane is stimulated. Specifically, the membrane potential goes from the resting potential (typically -70 mV) to some positive value (typically about +35mV) in a very short period of time (just a few milliseconds). Action potential occurs only when the membrane is stimulated (depolarized) enough so that sodium channels open completely. The minimum stimulus needed to achieve an action potential is called the threshold stimulus. 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. Polarization............................ Depolarization............................Repolarization Resting potential Action potential The permeability of the axon membrane to Na+ and K+ is regulated by gates, which open in response to stimulation. Net diffusion of these ions occurs in two stages: first Na+ moves into the axon. Then K+ moves out. This flow of ions, and the changes in the membrane potential that result, constitute an event called an action potential. The action of Na+ /K+ pumps , help to maintain a potential differences because , they pump out 3 Na + for every 2 K+ into the cell. As a result the Na+ became at high concentration in extracellular fluid than inside 1  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ the cell and K+ at high concentration within the cell. The physiologic ability of neurons and muscle cells to produce and conduct changes in membrane potential known as excitability or irritability. Changes in the potential differences across the membrane can be measured (by the voltage developed between 2 electrodes, one placed inside the cell, the other placed outside the membrane. The voltage between these 2 electrodes can be visualized by connecting them to an Oscilloscope. When the axon membrane has been depolarized to threshold level, the Na+ gates open and the membrane becomes permeable to Na+. Since the gates for the Na+ channels of the axon membrane are voltage- regulated, 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 indices a depolarization that opens even more voltage - regulated Na+ gates. 2  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ Since the myelin sheath prevents inward Na+ current. Action potential can be produced only at gaps in the myelin sheath called the node of Ranvier. This leaping of the action potential from node to node is known as Saltatory conduction. The How of the Action Potential 1. A stimulus opens the Sodium-Potassium Pump gates 2. Sodium gates open first, so positively charged ions flow into the axon, changing the membrane potential from -70 to +35mV 3. Membrane potential change is called depolarization, charge changes from negative to a positive 4. Potassium gates open second, so potassium flows out and the action Potential changes from +35 to - 70mV. 5. The resting potential resumes and this is called repolarization Other types of action potential in the human body: 1. Cardiac action potential: plays an important role in coordinating the contraction of the heart.The cardiac cells of the sinoatrial node (SA node) provide the pacemaker potential that synchronizes the heart. 2. Muscular action potential: the action potential in a normal skeletal muscle cell is similar to the action potential in neurons. Action potential result from the depolarization of the cell membrane (the sarcolemma) ,which opens voltage –sensitive sodium channels ; these became inactivated and the membrane is repolarized through the outward current of potassium ions. 3  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬  Refractory period: During the time that a patch of axon membrane is producing an action potential, it is incapable of responding – or refractory – to further stimulation. If a second stimulus is applied during the time that an action potential is being produced, the second stimulus will have no effect on the axon membrane.The membrane is thus said to be in a refractory period; it cannot respond to any subsequent stimulus.  Cable properties of neurons: The term cable properties refer to the ability of a neuron to transmit changes through its cytoplasm. These cable properties are quite poor because there is a high internal resistance to the spread of changes and because many charges leak out of the axon through its membrane.  Synapses: Is the functional connection between a neuron and a second cell? In CNS, this other cell is also a neuron. In PNS, this other cell may be a neuron or an effectors cell (gland or muscle). Synaptic Transmission: is the process whereby one neuron communicates with other neurons or effectors, such as a muscle cell. A typical neuron has a cell body; branching processes specialized to receive incoming signals (dendrites), and a single process (axon) that carries electrical signals away from the neuron toward other neurons or effectors. Electrical signals carried by axons are action potentials. Axons often have thousands of terminal branches, each ending as a bulbous enlargement, the Synaptic knob or Synaptic terminal. At the synaptic knob, the action potential is converted into a chemical message which, in turn, interacts with the recipient neuron or effectors. Synapses are junctional complexes between presynaptic membranes (synaptic knobs) and postsynaptic membranes (receptor surfaces of recipient neurons or effectors). The gap between them known as Synaptic cleft. Synaptic knobs contain many membrane-bounded synaptic vesicles, 40 to 100 nanometers in diameter, contain the Neurotransmitter. Synaptic knobs also contain mitochondria, microtubules, and other organelles. In brief, the impulses transmit from cell to another by 2 ways: 1. Electrical synapses (Gap junctions) 2. Chemical synapses (Neurotransmitters) Electrical Synapses (Gap junctions) Gap junctions are a specialized intercellular connection between multitudes of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulated gate between cells. One gap junction channel is composed of two connexons (or hemichannels), which connect across the intercellular space. Properties include: 4  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ 1. The presynaptic and postsynaptic membranes are partially fused. This allows the action potential to cross from the membrane of one neuron to the next without the intervention of a neurotransmitter. 2. Electrical synapses often lack the directional specificity of chemical synapses and may transmit a signal in either direction. 3. Gap junctions present in cardiac muscle, some smooth muscles, between glial cells and various regions in the brain. It is also present in embryonic tissue, but disappears as the tissue became more specialized. Chemical synapses (Neurotransmitters) Neurotransmitter include: Acetylcholine, Monoamines, Serotonin, Dopamine, and Norepinephrine, others (Amino acids, polypeptides and Nitric oxide). Action potentials arriving at synaptic knobs trigger the release of neurotransmitter into the synaptic cleft. Action potentials open calcium channels in the membrane of the synaptic knob, which causes an inward movement of calcium ions. Calcium ions trigger the release of neurotransmitter from synaptic vesicles into the synaptic cleft. The synaptic vesicles fuse with the presynaptic membrane during this process of exocytosis. The membranes of old vesicles become part of the presynaptic membrane and new vesicles pinch off from an adjacent area of membrane. These new vesicles are subsequently refilled with newly synthesized or "recycled". Once released into the synaptic cleft, neurotransmitters remain active until they are either altered chemically or taken back into the synaptic knob by special carrier systems and recycled. At cholinergic synapses, Acetylcholinesterase is present in the synaptic cleft. This enzyme cleaves the neurotransmitter into acetate and choline, neither of which is active. Serotonin and epinephrine, on the other hand, are taken up into the presynaptic terminal and recycled. 5  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ Lecture 4 / Muscular system The 3 types of muscle tissue are cardiac, smooth, and skeletal. 1- Skeletal muscle Each skeletal muscle fiber is a single cylindrical muscle cell. An individual skeletal muscle may be made up of thousands of muscle fibers bundled together and wrapped in a connective tissue covering. Each muscle is surrounded by a connective tissue sheath called the Epimysium.. Portions of the epimysium project inward to divide the muscle into compartments. Each compartment contains a bundle of muscle fibers. Each bundle of muscle fiber is called a Fasciculus and is surrounded by a layer of connective tissue called the Perimysium. Within the fasciculus, each individual muscle cell, called a muscle fiber, is surrounded by connective tissue called the Endomysium (see in figure 1). Skeletal muscle cells are multinucleated from the fusion of muscle cells. 2- Cardiac muscle Cardiac muscle is a type of involuntary mononucleated, striated muscle found exclusively within the heart. Its function is to "pump" blood through the circulatory system by contracting. Unlike skeletal muscle, which contracts in response to nerve stimulation, and like smooth muscle, cardiac muscle is myogenic, meaning that it stimulates its own contraction without a requisite electrical impulse coming from the central nervous system. A single cardiac muscle cell, if left without input, will contract rhythmically at a steady rate. This transmission of impulses makes cardiac muscle tissue similar to nerve tissue, although the cells are connected by Intercalated discs, which conduct electrical potentials directly, rather than the chemical synapses used by neurons. 3- Smooth muscle Smooth muscle is a type of non-striated muscle, found within the "walls" of hollow organs; such as the bladder, the uterus, and the gastrointestinal tract, and also lines the lumen of the body, such as blood vessels. Smooth muscle is fundamentally different from skeletal muscle and cardiac muscle in terms of structure and function. Smooth muscle is spindle shaped, and like any muscle, can contract and relax. In order to do this it contains intracellular contractile proteins called actin and myosin. While the fibers are essentially the same in smooth muscle as they are in skeletal and cardiac muscle, the way they are arranged is different. As non- 1  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ striated muscle, the actin and myosin is not arranged into distinct sarcomeres that form orderly bands throughout the muscle cell. The cells themselves are generally arranged in sheets or bundles and connected by gap junctions. In relaxed state, each cell is spindle-shaped, 25-50 μm long and 5 μm wide. The cells that compose smooth muscle have single nuclei. Table. Comparison of Muscle Types Characteristi Muscle Type c Skeletal Cardiac Smooth Nuclei Multinucleated; peripherally Single nucleus; centrally Single nucleus; located located centrally located Banding Actin and myosin form Actin and myosin form a Actin and myosin , NO distinctive bands distinctive bands distinctive bands Z disks Present Present Z disks not present; cytoplasmic dense bodies are present T tubules T tubules at A- junction; T tubules at Z disk; diads No T tubules; no triads or triads present present diads Cellular No junctional complexes Intercalated disks Gap junctions junctions Neuromuscul Present Not present; contraction is Not present; contraction is ar junctions intrinsic intrinsic, neural, or hormonal An aerobic High Low Low capacity Striation Striated Striated Not Striated Electrical Neurogenic Myogenic Neurogenic/Myogenic activity origin Presence Leg, Arm Heart Arterioles, Got Voluntary Involuntary Involuntary Muscle structure Looking at muscle anatomy shows that each muscle is made up of Muscle cells or (Myofibers). The functional characteristics of a skeletal muscle cell:  Each muscle cell (myofibers) is organized into sections along its length. Each section is called a Sarcomere and they are repeated right along the length of a muscle fiber. The sarcomere is the smallest contractile portion of a muscle fiber. 2  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬  The cell membrane is called the Sarcolemma, which is structured to receive and conduct stimuli.  The Sarcoplasm of the cell is filled with contractile Myofibrils or Myofilaments and this result in the nuclei and other organelles being relegated to the edge of the cell. Sarcoplasm contains glycogen, fat particles, enzymes and the mitochondria.  Muscle fibers (Myofibers) are grouped into bundles (of up to 150 fibers) called Fasciculi.  Myofibrils or Myofilaments are contractile units within the cell which consist of a regular array of protein myofilaments.  There are two types of protein filaments Actin and Myosin, which is run in parallel to each other along the length of the muscle fiber.  Myosin (1): is made of multiple molecules of a protein called Myosin. Each myosin molecule is composed of two parts: the globular "head" and the elongated "tail". They are arranged to form the thick filaments. The tiny globular heads protrude from the filament at regular intervals. These are called Cross bridges and play a pivotal role in muscle action.  Actin (2): is made of multiple molecules of a protein called Actin, which is composed of globular proteins (G actin units) arranged to form a double coil (double alpha helix) to form the thin filament. 3  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬  Each thin myofilament is wrapped by a tropomyosin (3) protein, which in turn is connected to the troponin (4) complex.  The sarcomere is often divided up into different zones to show how it behaves during muscle action. The Z-line separates each sarcomere. The H-zone is the center of the sarcomere and the M-line is where adjacent myosin filaments anchor on to each other.  The arrangement of the thick myosin filaments across the myofibrils and the cell causes them to refract light and produce a dark band known as the A Band. In between the A bands is a light area where there are no thick myofilaments, only thin actin filaments. These are called the I Bands. The dark bands are the striations seen with the light microscope.  As the sarcomeres contract the myofibrils contract. As the myofibrils contract the muscle cell contracts. And as the cells contract the entire muscle contracts.  Terminal cisternae: An expanded portion of the sarcoplasmic reticulum in which Ca +2 ions is stored during relaxation of the muscle.  Transverse tubules: (or T-tubule) is a deep invagination of the sarcolemma, which is the plasma membrane of skeletal muscle and cardiac muscle cells. These invaginations allow depolarization of the membrane to quickly penetrate to the interior of the cell Motor Units All motor neurons leading to skeletal muscles have branching axons, each of which terminates in a neuromuscular junction with a single muscle fiber. Nerve impulses passing down a single motor neuron will thus trigger contraction in all the muscle fibers at which the branches of that neuron terminate. This minimum unit of contraction is called the motor unit. Although the response of a motor unit is all-or-none, the strength of the response of the entire muscle is determined by the number of motor units activated. Each muscle cell is stimulated by a motor neuron axon. The point where the axon terminus contacts the sarcolemma is at a synapse called the neuromuscular junction. The terminus of the axon at the sarcolemma is called the motor end plate. Motor end plate : The specialized region of the sarcolemma of the muscle fiber at the neuromuscular junction , that surrounding the terminal end of axon. The neuromuscular junction is the synapse between the nerve fiber and muscle fiber. 4  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ Mechanism of Muscle Contraction 1. The axons of the nerve cells of the spinal cord branch and attach to each muscle fiber forming a neuromuscular junction. 2. An action potential passes down the nerve. 3. The nerve releases Ca++ that results in the release of Acetylcholine (ACh). 4. ACh binds with receptors and opens Na+ channels (Na+ Channels open and Na+ in).There is a decrease in the resting potential. 5. Na + rushes in and the sarcolemma depolarizes. 6. The positive patch in the membrane changes the adjacent patch of the membrane. Thus depolarization spreads. 7. Immediately after the action potential passes the membrane permeability changes again. Na+ channels close and K+ channels open. K+ rushes out of the cell. Cell reploraizes 8. Ca++ is stored in the sarcoplasmic reticulum. Depolarization releases the Ca++.The Ca++ clears the actin binding sites. 9. During muscle contraction the thin actin filaments slide over the thick myosin filament. When Calcium is present the blocked active site of the actin clears. 10. Myosin head attaches to actin. (High energy ADP + P configuration). 11. Power stroke: myosin head pivots pulling the actin filament toward the center. 12. The cross bridge detaches when a new ATP binds with the myosin. 5  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ 13. The end result is a shortening of the sarcomere. The distance between the Z discs shortens The H zone disappears, the dark A band increases because the actin & the myosin overlap more The light I band shortens. 14. Ca++ is removed from the cytoplasm. Tropomysin blocks the actin site. 6  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ Muscle twitch: A Myogram can record a twitch. There is a brief delay between the stimulation and the beginning of contraction, called the latent period. It corresponds to the change in Na+ and Ca++ ions occurring in the cell. In the second phase, the contraction phase, the muscle contracts. Myosin heads bind to actin and slide along it. It lasts 10-100 msec. The third phase or relaxation period lasts slightly longer than the contraction period. It corresponds to the calcium ions being shipped back into the sarcoplasmic reticulum. Shortly after initial stimulation, the muscle fiber cannot contract. It is the refractory period, lasting a short time in this muscle and is due to the depolarized state of the muscle membrane. 7  ‫ د شيماء رزاق‬: ‫اعداد‬ ‫المرحلة الثانية‬ The process of contracting takes some 50 msec; relaxation of the fiber takes another 50–100 msec. Because the refractory period is so much shorter than the time needed for contraction and relaxation, the fiber can be maintained in the contracted state so long as it is stimulated frequently enough (e.g., 50 stimuli per second). Such sustained contraction is called Tetanus. In the figure, · When shocks are given at 1/sec, the muscle responds with a single twitch.· At 5/sec and 10/sec, the individual twitches begin to fuse together, a phenomenon called Clonus or Summation. · At 50 shocks per second, the muscle goes into the smooth, sustained contraction of tetanus. Muscle fatigue: is a Physiological Inability of a muscle to contract. Muscle fatigue is a result of a relative depletion of ATP. When ATP is absent, a state of continuous contraction occurs. This causes severe muscle cramps. Fueling Muscle Contraction: ATP is the immediate source of energy for muscle contraction. Although a muscle fiber contains only enough ATP to power a few twitches, its ATP "pool" is replenished as needed. There are three sources of high-energy phosphate to keep the ATP pool filled.  Creatine phosphate  Glycogen  Cellular respiration in the mitochondria of the fibers. 8