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Neuronal Synaptic Transmission.pptx

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Neuronal Synaptic Transmission.pptx

  1. 1. Neuronal (Central) Synaptic Transmission • This is the chemical transmission of action potential from one nerve cell to the next one. • It consist of three components:- Presynaptic nerve terminal Synaptic cleft Post synaptic nerve cell • The transmission could be excitatory or inhibitory • The inhibitory could be post or pre-synaptic inhibitions.
  2. 2. EXCITATORY NEURONAL SYNAPTIC TRANSMISSION • When the AP reaches the pre-synaptic nerve terminal, it increases the permeability of the presynaptic membrane to Ca+ ions • This leads to Ca2+ ion influx. This Ca2+ ions then interacts with the synaptic vesicles to release an excitatory transmitter substance via exocytosis. • The excitatory transmitter substance released then diffuses across the synaptic cleft to combine with the sub-synaptic membrane of the post- synaptic nerve cells.
  3. 3. • This combination leads to increase in permeability to small ions which are K+, Na+ and Cl- across the membrane. • The membrane permeability changes then leads to generation of excitatory post-synaptic potential (EPSP). • EPSP is normally sub-threshold summation. When it comes to a threshold level by stronger stimulus, the EPSP leads to the generation of action potential which can be propagated along the post-synaptic nerve cell membrane.
  4. 4. • The excitatory neurotransmitter substances include:- Acetylcholine Noradrenaline or norepinephrine Adrenaline or epinephrine Dopamine Serotonin Aspartate Glutamate
  5. 5. INHIBITORY NEURONAL SYNAPTIC TRANSMISSION • As soon as the action potential reaches the pre-synaptic terminal, an inhibitory transmitter substance is released from the synaptic vesicles. • The particular inhibitory transmitter substance then diffuses across the synaptic cleft to combine with the sub-synaptic membrane of the post- synaptic nerve cells. • This combination then induces sub-synaptic membrane permeability changes. This leads to increase in the membrane permeability to Cl- and K+ ions.
  6. 6. • The membrane permeability changes then lead to production of inhibitory post-synaptic potential (IPSP). • IPSP is hyperpolarizing potential i.e. it is more negative than the resting membrane potential • Thus an action potential will never be produced. • This mechanism is often employed to suppress or inhibit or even abolished any unwanted messages or impulses or action potential.
  7. 7. • The inhibitory neurotransmitter substances include:- Glycine Gamma-aminobutyric acid (GABA) GIP (Gastric Inhibitory Polypeptide
  8. 8. Neuronal Transmission Neuromuscular Transmission 1. The transmission can be excitatory or inhibitory 2. The excitatory transmitter substance include Ach, adrenalin, noradrenalin, dopamine, Serotonin, while the inhibitory transmitter substances include GABA and glycine. 3. When transmitter substance combines with sub-synaptic membrane of post- synaptic cell, it induces the permeability changes to K+, Na+ and Cl- ions. 4. EPSP is normally sub-threshold but may reach threshold level by more stimulus 5. This is not the case in nerve-nerve junction The transmission is excitatory The transmitter substance is Ach. It induces permeability changes to Na+ and K+ EPP normally reaches threshold There is always one pre-synaptic terminal per muscle fibre. Differences Between Neuronal And Neuromuscular Synaptic Transmission
  9. 9. Neuromuscular Junction • Neuromuscular junction is a junction between a muscle and a nerve • It has three components: - A pre-synaptic nerve terminal - A gap (synaptic deft) - A Post-synaptic cell (skeletal muscle cell) • The pre-Synaptic nerve terminal contains synaptic vesicles • The synaptic vesicles contain acetylcholine, a transmitter substance
  10. 10. • Post synaptic cell is made up of the sub-synaptic membrane of the post- synaptic cell. • Receptors are located on the sub-synaptic membrane. Neuromuscular Transmission • This is the chemical transmission of A.P from the pre-synaptic terminal across the synaptic cleft to the post-synaptic cell element (skeletal muscle cells)
  11. 11. Mode of Transmission • As soon as the A.P reaches the pre-synaptic terminal, it increases the permeability of the pre-synaptic membrane to calcium ions (Ca2+) • This leads to calcium ions influx • The calcium ions combine with synaptic vesicles to release the transmitter substance, acetylcholine into the synaptic cleft by exocytosis. • Acetylcholine then diffuses across the synaptic cleft to combine with the sub-synaptic membrane of the post-synaptic cell i.e skeletal muscle.
  12. 12. • This induces permeability changes of the sub-synaptic membrane to small cations namely sodium and potassium ions. • Thus then leads to generation of end-plate potential (EPP) • If the EPP reaches threshold of which it normally does, an AP is now produced on the post-synaptic membrane of the muscle. • Some of the muscle soon contracts.
  13. 13. Fate of Acetylcholine • Acetylcholine combines with the receptors on the sub-synaptic membrane only for a short time, 1-2 seconds • It is soon broken down by the enzyme cholinesterase into two inactive components – choline and acetic acid. • Choline and acetic acid are reabsorbed by the pre-synaptic terminal. • In the presence of choline-acetyl transferase, the two combine to form acetylcholine. • Acetylcholine is then stored in the vesicles until another A.P comes along, and the whole process is repeated again.
  14. 14. Miniature End-Plate Potential (mEPP) • This is also known’s as quanta release of acetylcholine. • In the resting state, packets or quanta of acetylcholine are released randomly from the synaptic nerve terminal. • Each packet produces a miniature polarization called mEPP. • The amplitude of EPP is of the order 0.5-1.0mV. • The number of quanta released and hence the amplitude of the potential produced is increased in the presence of Ca2+ and reduced by magnesium ions (mg2+). • EPP is an integral multiple of mEPP
  15. 15. Muscular System General Functional Characteristics of Muscles • Muscle has four major functional characteristics: Contractility (Shorten forcefully) Excitability (Responds to stimuli) Extensibility (Can be stretched) Elasticity (Recoils to resting length) • There are three kinds of muscle in the body: Skeletal, Smooth and Cardiac. • They are classified according to their structure and function.
  16. 16. Skeletal Muscle • Makes up the bulk of muscle in the body, accounts for approximately 40% of body weight. • Skeletal muscle is composed of large muscle fibres. • Each muscle fibre is a long, cylindrical cell. • Under the microscope, skeletal muscle cells are multinucleated cells that appear striped/striated (presence of thin light and dark bands (Striations) that lie across fibres). • Function is mainly under voluntary/conscious control by the nervous system
  17. 17. Skeletal Muscle • These functions include: Locomotion Facial expression Posture and Many other body movements • Each muscle consists of numerous intermingled motor units • A Motor unit is the basic unit of contraction in an intact skeletal muscle. • The motor unit is composed of a group of muscle fibres that function together and the somatic neuron the controls them.
  18. 18. • A muscle fibre is a single cell consisting of a cell membrane (sarcolemma), cytoplasm (sarcoplasm), several nuclei and myofibrils. • Each myofibril is composed of various thick (myosin) and thin (actin) filaments • One muscle fiber contains around one thousand or more myofibrils and each myofibril has several repeating contractile structures, called sarcomeres. • The sarcomere is the contractile unit of skeletal muscle. it is the repeating unit between two z-lines. • Z-lines: the zig-zag protein structures which serve as attachment sites for the thin filaments • M-line: proteins which form attachment sites for the thick filaments.
  19. 19. • I-band: light bands of sarcomere (i.e. regions occupied by thin filaments). • A-band: dark bands of the sarcomere (i.e. contains more thick filaments: at the outer edges of the A-band the thick and thin filaments overlap). • H-zone: middle zone of the sarcomere. • Sarcoplasmic reticulum: a modified endoplasmic reticulum which wraps around each myofibril. • Transvers (T) tubule: branching network which allows the action potentials to move rapidly from cell surface to the interior of the muscle fiber.
  20. 20. Neuro-Muscular Junction • The synapse of a somatic motor neuron on a muscle fiber is called a ‘Neuromuscular junction’. • When Action potential propagated in the motor neuron reaches the axon terminal it causes voltage-gated calcium channels to open and calcium flow into the cell • The increase in intracellular calcium causes exocytosis of synaptic vesicles (releasing Acetylcholine (Ach) into the synaptic cleft).
  21. 21. Neuro-Muscular Junction • Ach binds to nicotinic receptors (ligand-gated, non-specific cation channels) on the motor end plate (postsynaptic membrane of the skeletal muscle fiber) • Sodium enters cell and causes an end plate potential or graded potential. • Local current spreads from the end plate in both directions, causing the opening of the voltage-gated sodium channels and sodium enters the cell and an AP is generated. The AP cause contraction of the skeletal muscle cells. • Ach acting on a skeletal muscle motor end plate is always EXCITATORY and causes a contraction.
  22. 22. Skeletal Muscle Action Potential • The skeletal muscle AP looks similar to the AP in a neuron, except for the RMP [neuron = - 70mV; skeletal muscle = -90mV]. • The RMP of skeletal muscle is more negative than that of a neuron, since skeletal muscle is less permeable to Na+ • Skeletal muscle also has a different threshold potential to the neuron (threshold potential in skeletal muscle = between – 75 and – 70mV; threshold potential in neuron = - 50mV).
  23. 23. Mechanism of Muscle Contraction • The ionic basis is similar to that in nerves, but the major contributor to repolarization is chloride ions influx, rather than K+ efflux. • Contractions are initiated and maintained by the transmission of A.P.s from the motor nerve to the muscle. • The EPP generated by the interaction of released acetylcholine and acetylcholine (nicotinic) receptors initiate an A.P at the sarcolemma surrounding the end plate. • Once initiated in the middle of each muscle fibre, the action potentials are conducted at about 4-5ms towards both ends of the fibre by the local current flow, as in unmyelinated axons. • When the A.P is on the membrane, it spreads inwards by means of the transverse tubule.
  24. 24. Mechanism of Muscle Contraction • This A.P excites the terminal cisternae to release calcium ions leading to an increase in intracellular concentration of calcium ions. • The calcium ions then combines with troponin C, and this leads to two major changes mainly: (i) Removal of inhibition by troponin I on actin, to expose the active site of actin. This leads to the actin being activated. (ii) It also leads to lateral displacement of tropomyosin, uncovering the active site of myosin i.e myosin is now activated. • Thus the diffusion of the calcium ions to the myofilaments and binding to troponin causes tropomyosin to move and expose actin to myosin.
  25. 25. Mechanism of Muscle Contraction • Both actin and myosin combine forming linkages across each other. • The actin molecules slide in between the myosin molecules this leads to shortening of the sarcomere or muscle length which is what is known as CONTRACTION. • This event is known as the SLIDING FILAMENT THEORY • Energy in the form of ATP is required for muscle contraction.
  26. 26. Muscle Relaxation • Relaxation occurs when calcium is taken up by the sarcoplasmic reticulum, ATP binds to myosin and tropomyosin moves back between action and myosin. • The calcium ions are first pumped back in to the longitudinal portion of the sarcoplasmic reticulum. • The Ca2+ then diffuse into the terminal cisternae from the longitudinal portion of the S.R. this then lead to a reduction in intracellular Ca2+ concentration. • The combination of Ca2+ with troponin C seizes or stops, leading to relaxation of the muscle as the inhibition which troponin I has on actin is restored. • So, tropomyosin moves back to its original position to cover up the active part of the myosin. This is known as MUSCLE RELAXATION. • Relaxation also requires energy in form of ATP
  27. 27. Types of Muscle Contraction Isotonic Contraction: An isotonic contraction is one that causes a change in muscle length but no change in muscle tension. Isometric Contraction: Is one that causes a change in muscle tension but no change in muscle length. Muscle Tone: This is the maintenance of a steady tension for long period of time. Asynchronous Contraction: This is the production of smooth steady muscle contractions by motor units.
  28. 28. MUSCLE TWITCH (Excitation-Contraction Coupling) • Excitation-contraction coupling is the process in which muscle action potentials initiate calcium signals that in turn activate a contraction-relaxation cycle. • In an intact muscle, one contraction-relaxation cycle is called a muscle ‘twitch’. • Thus when a muscle is excited by a single action potential, it contracts and then relaxes (muscle twitch), and it has a latent period (lag), contraction and relaxation phases.
  29. 29. Tension-Length Relationship • This is the direct relationship between the tension and length • The force of contraction is proportional to the length of the muscle fibre. • This r/ship is dependent on contracting muscle fibre length and the velocity of contraction. • Muscle contracts with less than maximum force if its initial length is shorter or longer than optimum. • The length-tension relation can be explained using the sliding filament theory i.e the mechanism of muscle contraction. • When a muscle fibre contracts isometrically, the tension developed is proportional to the number of cross linkages between the actin and myosin molecules.
  30. 30. • When the muscle is stretched, the overlap or the number of cross linkages between actin and myosin is reduced • Because of this, the maximal tension will always be reduced. • When the muscle is shorter than the resting length, the actin filament overlaps • This leads to interferences thereby reducing the number of cross-linkages between actin and myosin with consequent reduction of the maximum tension developed by the muscle.
  31. 31. TETANUS • A rapidly repeated stimulation or rapid frequency of stimulation such that contraction occurs without adequate time for relaxation, the responses will appear to fuse into one continuous contraction. This is known as TETANUS. Types • Incomplete Tetanus:- This occurs when there are incomplete period of relaxation between periods of contraction. It is an incomplete fusion of individual twitches. • Complete Tetanus:- This occurs when there is no relaxation between contraction and complete fusion occurring. The muscle tension developed during complete tetanus is about 4 times that developed by the individual twitch contraction. • The frequency of contraction controls tetanus and when this is constant, the muscle appear to be in a sustained state of contraction.
  32. 32. Muscle Fatigue • If the rate of stimulation is prolonged, the twitch responses soon begin to grow weaker and weaker, and eventually fall to zero. • This fall in tension following prolonged stimulation is referred to as muscle fatigue. • Thus fatigue is the decreased ability to do work and can be caused by: central nervous system (psychological fatigue) depletion of ATP in muscle (muscular fatigue) depletion of acetylcholine in the neuromuscular synapse (synaptic fatigue)
  33. 33. • Fatigue can occur both at high and low frequency of stimulation but of course, fatigue will be quickly reached if the frequency is high. • When the muscle is completely fatigued and unable to develop tension, the concentration of ATP in the muscle is very low. • During recovery, the ATP concentration rises as metabolism replaces the ATP broken down during contraction.
  34. 34. Muscle Types There are different types of muscle classification: 1st Classification A-Type:- The muscles are large and pale. They contain relatively little mitochondrial adenosine triphosphate. C-Type:- They are small and dark. They contain large quantities of ATP B-Type:- These are intermediate, both in size and ATP content compared to A and C types.
  35. 35. 2nd Classification Red (Slow) twitch fibre (Type 1):- They are slow and contain B fibres, they are darker compared to the white muscle Properties They respond slowly They split ATP slowly and have a well developed blood supply, many mitochondria and myoglobin. They have longer latent period They are adapted for long slow posture maintaining contractions e.g the long muscle of the back including the gluteus muscle.
  36. 36. White (fast) twitch Muscle (Type 2):- They contain A, B or C fibres, thus are pale or white in colour. They split ATP rapidly and do have very short twitch duration, thus its name fast muscle. They are specialized for skilled movement e.g ocular muscle of the eye and the entire finger muscles. There are two types of fast/white muscle: Fast-twitch, fatigue-resistant fibres:- These have a well developed blood supply, many mitochondria and myoglobin. Fast-twitch, Fatigable fibres:- These have large amounts of glycogen, a poor blood supply, fewer mitochondria and little myoglobin.