Nerve and Neuromuscular Junction PDF

The Nerve physiology Presented by: Dr. Yasmine Gamal Sabry Lecturer in the physiology department, faculty of medicine, Ain Shams university 1  STRUCTURE OF THE NEURON It is composed of three...

The Nerve physiology Presented by: Dr. Yasmine Gamal Sabry Lecturer in the physiology department, faculty of medicine, Ain Shams university 1  STRUCTURE OF THE NEURON It is composed of three major parts: 1. The soma, which is the main cell body of the neuron 2. A single axon, which extends from The soma into a peripheral nerve that leaves the spinal cord 3. The dendrites, which are great numbers of branching projections of the soma. Dendrites receive impulses and conduct them toward the cell body. 2  Types of nerve axons Myelinated nerves Unmyelinated nerves  Myelin is a protein-lipid complex that is wrapped around the axon.  The myelin sheath envelopes the axon EXCEPT at its ending and at the nodes of Ranvier.  The myelinated nerves are Faster in impulse conduction and More Economic in energy consumption than unmyelinated fibers 3  Properties of Nerves Chemical Thermal Electrical Mechanical 1- Excitability: it’s the ability of the nerve to respond to various stimuli. What is stimulus? It is any change in the internal or external environment surrounding the excitable tissue (nerve or muscle) that causes it to react. It can be: Electrical, Chemical, Mechanical, OR Thermal 4 2- Conductivity: the change produced by stimuli (nerve impulse) is rapidly conducted along the nerve fiber. 3- All or none law: “Threshold” (minimal stimulus needed to excite the nerve), produces a maximal action potential. 4- Adaptation: the nerve quickly adapts to the stimulating current. 5- In fatiguability: nerves are not fatigued by repeated stimulations. 5  Basic Principles of Electricity: - Potential difference: “The difference in the amount of charge between two points”. - Membrane Potential: Difference in charge on both sides of the nerve membrane. - Resting membrane potential: It is the potential difference across the membranes of excitable tissues (nerve/ muscle) during rest. 6  Distribution of Major Mobile Ions Across the Plasma Membrane of a Typical Nerve Cell There are differences in the composition of the extracellular and intracellular fluids. Due to the distribution of these charged ions ➔ the inside of the cell membrane is relatively negative to the outside during rest (absence of stimuli). 7  Resting membrane potential (RMP)  It is the potential difference between the inner and outer surfaces of the cell membrane of excitable tissues during rest. Values:  Nerve fibers: -70 m V.  Skeletal and cardiac muscle fibers: -90 m V. Causes: Unequal distribution of ions across cell membrane in extracellular fluid and cytoplasm 8  Causes of Unequal Ion distribution 1- Selective membrane permeability (93%) 2-Na+/K+-ATPase pump (7%) During rest the membrane Intracellular non-movable is more permeable to negatively charged Electrogenic pump that potassium ions (K+) more proteins: the proteins in pumps 3 Na+ out of the than sodium ions (Na+), the inner surface of the cell cell and 2 K+ ions into since K+ leakage channels membrane is negatively the cell, helping in 50-70 times > Na+ leakage charges, and can’t move maintaining RMP channels due to its large size. 9  Resting membrane potential(RMP) Since more positive ions (K+) are pumped outside than inside (Na+) via leakage channels. Also the action of Na+/K+ ATpase pump, Which leads to negativity inside and positivity outside the cell. 10  Types of membrane potential Polarized state (RMP): It is the membrane potential during rest (-70mv), the inside is relatively more negative than the outside of the membrane. Depolarized state (depolarization): It is reduction in membrane potential negativity (-60, -50, -40….mv), it can also, include events in which the membrane potential reverses and moves above zero to become positive (+10, +20,…mv). Hyperpolarized state (hyperpolarization): It is increase in membrane potential negativity (-90, -100, -110,….mv), the inside of the membrane becomes more negative than the value of the RMP. 11 12  The action potential The action potential is a transient reversal in the membrane polarity of an excitable cell (nerve or muscle) in response to threshold stimulus. What is threshold stimulus? The minimum stimulus needed to achieve an action potential. 13 Phases of Action potential 1- Depolarization 2- Repolarization 3- Hyperpolarization 4- Back to RMP  1. Depolarization: The initial 15 mV of depolarization, the rate of depolarization slow. Then the rate increases at a point called the firing level (-55mv). At this point, voltage-gated sodium ion channels open. Sodium ions rush in a Positive feedback mechanism. The membrane potential changes from -70mV to +35mV (Reversal of polarity) 15  2. Repolarization:  Sodium ion channels close.  There is opening of voltage-gated potassium ion channels K+ ions rush out of the cell by its concentration gradient, repolarizing the membrane.  When it is about 70% completed, the rate of repolarization decreases and becomes more slowly 16 4. Hyperpolarization:  After reaching the previous resting Hyper- polarization level, the tracing overshoots slightly in the hyperpolarizing direction.  It is of small amplitude (1-2 mv) but prolonged in duration (40 ms)  The opening of voltage gated K⁺ channel is slower and more prolonged, that when RMP is reached, Some K⁺ channels are still open with slow return to the closed state. 17 4- Back to RMP The RMP is finally reached when the K⁺ channel is completely closed, and the normal Hyper permeability is regained. polarization Any excess Na⁺ inside or any extra losses of K⁺, due to repeated stimulation of the membrane, are adjusted by Na⁺- K⁺ pump. 18  Excitability changes during action potential (1) Absolute Refractory Period : In this period the nerve is unexcitable. No stimulus can excite it, whatever its strength. It corresponds to ascending limb of A.P. and the upper l/3 of descending limb (2) Relative refractory period: In this period the excitability is partially recovered. It corresponds to the remaining part of descending limb of A.P.  The Local (graded) potential Local potentials could be induced by SUB-THRESHOLD stimulation of excitable membranes of the nerve and muscle fibers. Local potentials are physiological responses in the following sites Sensory receptors Synapses Neuro-muscular junction 20  Characteristic features of local potential 1. Local potentials are important in Short distance signaling function 2. Its magnitude is proportionate to the strength of the stimulus = Graded response (Amplitude-modulated) 3. It decays with distance from the initial site= Decremental conduction 4. It is localized to the area of stimulation= Non- propagated 5. It can be summated when another stimulus is applied 6. It occurs due to opening of non-voltage gated channels 7. It can be Excitatory or Inhibitory 21  Nerve Conduction It starts at the axon hillock and passes quickly along the axon. According to the type of nerve, conduction is classified into: 1- Point to point conduction 2- Saltatory conduction 22  Conduction in unmyelinated & myelinated nerves Unmyelinated Myelinated Myelin sheet Absent Present Type Point to point Saltatory conduction conduction Speed Slow Fast Energy High energy More economic consumption Occurs in All over the nerve Only at the Nodes of membrane Ranvier 23  Neuro-muscular transmission Release of acetyl choline 24 Destruction of the Released Acetylcholine by Acetylcholinesterase. The acetylcholine, once released into the synaptic space, continues to activate the acetylcholine receptors as long as the acetylcholine persists in the space. However, it is removed rapidly by two means: (1) Most of the acetylcholine is destroyed by The Enzyme Acetylcholinesterase (2) A small amount of acetylcholine diffuses out of the synaptic space The rapid removal of the acetylcholine prevents continued muscle re- excitation after the muscle fiber has recovered from its initial action potential. 25 26  Properties of neuromuscular transmission (NMT) 1-Unidirectional: from nerve to muscle and not the opposite. 2-Delay: there is a delay 0.5 msec between the nerve impulse reaching the neuromuscular junction and the action potential generated in muscle. 3-Can be fatigued: due to depletion of acetylcholine vesicles. 3-Effect of ions: Calcium influx will stimulate NMT as it helps the acetylcholine vesicles to rupture, while magnesium will inhibit it as it stabilize the vesicles.  Drugs that enhance neuromuscular Drugs that block neuromuscular transmission: transmission: Acetylcholine like drugs, eg. Curare: antagonize the action of Ach Carbacol by occupying its receptors at motor Anti-choline esterase drugs: end plate Short acting: eg. Neostigmine Botulinum toxins: It blocks the release of Ach from the nerve Long acting: eg. Organophospherous endings compounds (DFP, pesticides) Causes irreversible inhibition of Choline esterase enzyme resulting in persistent depolarization & muscle paralysis 28  Myasthenia gravis It causes muscle paralysis because of inability of the neuromuscular junctions to transmit enough signals from the nerve fibers to the muscle fibers. It is believed that myasthenia gravis is an autoimmune disease in which the patients have developed antibodies that block or destroy their own acetylcholine receptors at the postsynaptic neuromuscular junction. The end plate potentials that occur in the muscle fibers are too weak to initiate opening of the voltage-gated sodium channels so that muscle fiber depolarization does not occur. 29  Myasthenia gravis If the disease is intense enough, the patient dies of paralysis—in particular, paralysis of the respiratory muscles. The disease can usually be ameliorated for several hours by administering neostigmine or some other anticholinesterase drug, which allows larger than normal amounts of acetylcholine to accumulate in the synaptic space. Within minutes, some of these paralyzed people can begin to function almost normally, until a new dose of neostigmine is required a few hours later. 30 Faculty of Physiotherapy 31