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1 General discussion about the last lecture: Q: In graded potential, does the number of terminals matter in generation the graded potential, i.e. if we have 2000 terminals or 120 terminals, does it different? And what is different when they reach the brain? A: Yes, it s how the brain can distinguish between light wound and harm ones, to decide if it is mild, moderate or severe, depending on the magnitude of the graded potential. {Check the slides} The frequency of action potential depending on the magnitude of graded potential, when the magnitude of graded potential becomes high, the frequency will raise (the brain will receive 1000 AP/s instead of 10 AP/s for example). {Check the slides} In very intense cases (square potential), it s because of Lengthy AP, the frequency will raise (10000 instead 1000 for example). When there are a patient in a pain, we ask him to grade his pain in scale from 1-10, his choice will give an indication about the problem. Because the pain is subjected, for example: 3\10 will indicate something totally different from 9\10. So, the magnitude of graded potential definitely will affect the frequency of action potential. Page 1

2 Note: the action potential is Over-none activity, so the amplitude of it doesn t change. On the last lectures we talked about action potential and graded potential, today we are going to talk about one type of graded potential which is compound graded potential (CP), recorded from ulner, radial, or median nerve. Compound graded potential(cp): summation of so many graded potentials that all of them reached the threshold. We should know how to read the ENG(Electroneurogram), IN ENG we can test motor fibers or sensory fibers. Sensory fibers: There are orthodromic method and antidromic method. Orthodromic: when we generate a compound potential somewhere (tip of the finger), and record the frequency just proximal to it (on the elbow or wrist for example), its physiological (normal way). They found that when we record the frequency in ortodromic, it s not obvious and it disappears by the electrical noise from the environment. So they decided to use antidromic. Page 2

3 Antidromic (against physiology): when we generate a compound potential somewhere (the wrist or elbow), and record the frequency just distal to it. they found that the frequency will be very obvious and clear. Why?? A: Because on the tip of the finger, the nerve is more subcutaneous, while in the arm or forearm there are a lot of muscles, and fats that would disturb the recording process. Motor fibers: We stimulate a compound potential, and record it again somewhere else. In recording the stimulation here in motor fibers we aiming to measure the conduction velocity (is it normal or not). We generate a compound potential in 2 different sites(elbow and wrist for example), and record it in one place (in the palm of the hand). Which one will be recorded first?? A: Of course the one comes from the wrist because it s closer. {Check the slides} When we record the CP(Compound potential) for the wrist, there will be small distance before the recorded CP, and it s a small one, but when we record the CP that comes from the elbow there will be a longer distance till the recorded CP, because the elbow is further than the wrist. Page 3

4 We know that velocity= distance/time While: The distance: from the chart, it s the distance between the wrist and the elbow (mm) Time: from the chart, the time until recorded elbow s CP time until recorded wrist s CP, (PS: its more obvious in the slides, so go back and check it there) In ENG we diagnose 2 important cases, the total and partial axonal lost (partly lose the nervous conduction ), and the demyelination. {Check the figure} - The first case is a normal records, the second one is for a patient and the third one is for another patient. CP comes from wrist - The first recorded CP is for the Wrist, and the second is for the elbow. CP comes from elbow Case 1 - The second case shows that the distance until recording the Wrist s CP is elongated > the velocity has been decreased> there are a loss of myelin > demyelination. (This case is typical and very common) Case 2 Case 3 Page 4

5 - What about the elbow s CP record! Is it elongated? This means what? What is happened to the amplitude? We see here that the amplitude is smaller, and the distance is longer than normal. A: Small amplitude indicates damage in some of the axons> so partial axonal damage (loss) in between the wrist and the elbow. Elongation in the CP indicates demyelination. - The third case indicate a partial injury in the nerve. Note: in case of total axonal damage we will have a straight line, and no CP Remember the demyelination effect the conduction velocity of the nerve. - Inching technique: diagnose a nerve for paralysis inch by inch, to spot the place of the axonal damage exactly. When we have a patient with right hand injury, we have to test both hands, the right to diagnose the injury, and the other one to compare with. {Check the slides} this is a patient with ulnar nerve injury, and its records. According to the records WHAT IS THE DIAGNOSE DOCTORS A: Right hand abnormality, above the elbow (the CP records above the elbow show abnormality). Left ulnar is normal Page 5

6 We talked about the electrical signals in the soma, dendrites, all the way in the axon to the terminals, So what happens when it reaches the terminals? Sometimes we need to convey the information from periphery to the center involving more than one neuron, and convey orders from the brain to the muscles involving more than one neuron, there must be a connections, this what we call synapses. Synapse: is a junction that permits a neuron to pass an electrical or chemical signals to another neural cell. The signal goes from the axon to the terminals releasing the neurotransmitters, which go and bind(sit) on a highly specificc receptors on the surface of the target cell. Note: if any other substance bind (sit) on this receptor, it won t initiate the same effect that would happen if the neurotransmitter did, because of the specificity of the receptors. Page 6

7 There are 2 types of synapses: 1. electrical synapse>> in form of a gap junction {Check the slides} -small tubes in between the adjacent cells,that allow ions to enter from right to left,and from left to right (bidirectional). -there are electrical synapses in the olfactory pathway. 2. chemical synapse>> we are going to study it. Note: 99.9% of synapses in the brain are chemical synapses. Why? A: Because in the brain we need a controlled signals not signals which going without any control, and the signals in the brain are directed. Chemical synapses are responsible for all the psychological diseases, and a lot of neurological diseases. When we go back to brain, we know that there are about 100 billion cell, and each one has about synapse, each synapse has at least 2or3 neurotransmitter. So we are going to study the synapses in the muscles (it s more simple and have the same structure). Note: we have about 270 muscles in our body, and all of the neuromuscular junctions are the same structure. Page 7

8 In the neuromuscular synapse: -the region where the terminals of neuron attach to the muscle are modified, and called motor end-plate. -there are a vesicles holding the Ach neurotransmitter in the neuron terminal. Q:what do we need in order to release Ach from the neuron terminals?? A: action potential and Ca ions. When the action potential reaches the terminal, the Ca channels open, leading to Ca ions influx, these Ca ions combined with proteins leading to approaches of Ach vesicles to the terminals and rupture. The action potential when reaches the terminals, it causes a rupture of about 125 vesicle, each vesicle has Ach molecules. {Check the slides} What about the channels ( Ach receptors)? - It s a protein structure travels along the plasma membrane, usually its closed, and need 2 Ach molecules to open. - When it is opened, Na ions influx happens, depolarization then graded potential happens we call it end plate potential. - This action potential distribute along the muscle causing this muscle to contract. -If the Ach remains on the receptors, it will cause a spastic without any relaxation, so there should be something to stop this Ach!!What is it? Page 8

9 A: Its Ach esterase >> stops the function of Ach, makes the neuromuscular junction fresh and free to have another action potential {Check the slides} So we can control our muscles (voluntary muscles), even if we are sleeping The inventions and drugs : *causing muscle contraction (spasm). - increase Ca concentration - stop the Ach esterase: the Ach won t be removed and the muscles will stay contracted. nerve gas (diiso propyl fluorphosphate): stops the Ach esterase enzyme, so the Ach will stay connected to the receptors,it cause spasm,and stop breathing, very painful way to die, there isn t any treatment for this gas. Some scientist used drugs to inhibit Ach esterase in order to improve muscles weakness, in case of myasthenia gravis which makes antibodies kill the receptors (usually affect females), *causing muscle relaxation. - prevent the release of Ach they used a bacteria ( botulinum toxin : it s a bacteria found on the rusty cans, causes gastroenteritis and paralysis by prevent the release of Ach from the terminals) for the first time in medicine, and extracted The active compound from it, so they made a controlled muscle relaxation drug (BOTOX), Botox used to decrease the wrinkles in the human skin. Page 9

10 Note: Botox used only on cholinergic sympathetic cells, for example its used to prevent the sweating under the armpit, especially for surgeons., -competitive antagonist: substances bind the Ach receptors and prevent Ach from binding. American Indians الحمر) (الهنود used this for hunting, by soaking the arrows in a plant called Curari, this plant causes paralysis,. - curari used as a muscle relaxation in some operations (in case of high tense muscles contraction in the place of the surgery) - close Ca channels Enjoy Done By: Anas I. Amayreh Page 10

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