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BIOPHYSICS OF THE NERVOUS SYSTEM

BIOPHYSICS OF THE NERVOUS SYSTEM. Prof. Dr. Metin TULGAR. A General View to the Nerveous System. There are billions of cells in the nervous system. Of course, it is essential to know the nerve cells to understand the underlying construction and mechanisms of the system.

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BIOPHYSICS OF THE NERVOUS SYSTEM

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  1. BIOPHYSICS OF THE NERVOUS SYSTEM Prof. Dr. Metin TULGAR

  2. A General View to the Nerveous System There are billions of cells in the nervous system. Of course, it is essential to know the nerve cells to understand the underlying construction and mechanisms of the system. But, to avoid missing the actual whole system, better to start with a general view. We must be aware of the forest first, before we see only one tree.

  3. Its duties: • Take care of the body, • Protection of the body, • Functions of the body. Its product: • Performance of the body (behaviour of man) Since it has such important responsibilities, it is normal that it has a complicated structure.

  4. Functional Organization of the Nervous System the nervous system central nervous system (CNS) peripheral nervous system (PNS) efferent pathways afferent pathways somatic system (voluntary) “musculoskeletal” autonomic system (involuntary) “visceral motor neurons” parasympathetic nerves sympathetic nerves

  5. Anatomy and Physiology of the Nervous System sensory cortex brain III thalamus spinoreticular tract II PNS CNS action potential synapse I receptor peripheral nerves; cervical – 8 pairs, thoracic – 12 pairs, lumbar – 5 pairs, sacral – 5 pairs, cocygea – 1 pairs, in total – 31 pairs. interneuron

  6. Nerve Cells • Glia • Neuron

  7. astrocytes Oligodendracytes Gliassmaller in size compared to neurons, but they are 10 times greater in number. Half of the brain is covered by glias.Their functions are not exactly known; however, it is clear that they provide constructional support for the neurons by means of Schwan cells producing myelin.There are two sorts of glias, in general:

  8. Glial cellshelp neurons stay healthy. If neurons are dying, restoring glial cells could be the key to survival

  9. As known, there are billions of cells in the human body, and every single neuron has an electrical activity as long as it is alive. The basic difference between glias and other cells is that the neurons, under cirtain circumstances, are able to conduct their electrical activity to neighbouring neurons.Consequently, neurons are considered as functional units of the nervous system.

  10. Glial Cell Types by Location and Basic Function

  11. The Neuroncomposes of two morphological region: • 1) soma, • 2) fibre; • I) axon • II) dendrites.

  12. soma axon receptor dendrite

  13. Somas are called as laminae in the cortex and cerebellum of the brain, and ganglion outside the central nervous system.Laminas are located in the form of sheets, ganglions in wide nodules. These groups form grey matter in the brain and butterfly or H-shaped forms in the middle region of spinal cord.In the rest of places of the central nervous system, they form white matter.

  14. Axon is a single fiber. Their length depends on the location, sometimes being longer than 1 m. Axons conduct nerve impulses.In the brain, there are about 10 billions of axons, and in the dorsal column, more than 1 million.

  15. An axon can be resembled to a cylindirical tube. Intracellular fluid (axoplasm) is separated from the extracellular fluid by a very thin membrane. membrane extracellular fluid intracellular fluid (axoplasm)

  16. In the end of axons, there are receptors which are bare nerve endings.

  17. Diameters of axons: 0.5 - 20 μm In myelinated axons; conduction velocity is approximately proportional to the diameter:v ~ DIn the non-myelinated fibers; with square root of the diameter:v ~ √D

  18. Classification of Axons function type diameter (μm) conductivity (m/s) 12 - 20 somatic motor A-α 70 - 120 5 – 12 “thick myelinated” A-β 30 – 70 “rapidly conducting” connected to low-threshold receptors (sensitive to light mechanical stimuli) 3 – 6 “thin myelinated” A-γ motor neuron connected to muscle spindles 15 - 30 A-δ 2 - 5 12 - 30 (sensitive to cold, pinprick and needling) B preganglionic autonomic < 3 3 - 15 C 0.3 – 1.3 0.7 – 2.3 post ganglionic autonomic 0.5 – 2 “slowly conducting” connected to high-threshold receptors (responsible for pain transmission) C 0.4 1.2

  19. MyelinAlipid substance covering the axon along the membrane.It is not contineuosly located, there are gaps of 1-2 μm called Ranvier nodes in every 1-2mm. Functions like a kind of electrical isolator to increase capasitive effect of the neuron, and also its conductivity. In accordance with the equation,XC = 1/ωC = 1 /2πfC as the myelin gets thicker, capasitive reactance decreases.Considering Ohm’s Law;i = V/XCthe conductivity of axon for transmitting of nerve impulses increases.

  20. Dendritesshort branches along the axon.Numerous in number.They increase the surface of the neuron to facilitate the communication with neighbouring neurons.Some neurons have dendritic contacts ofup to60000.

  21. Synapse Sherrington & Lord Adrian, 1921Nobel Price in Medicinea very narrow gap (200 - 300 Å) between two neurons.provides the connection for nerve impulses to be transmitted.During this transmission,active neuron sending signal is called presynaptic neuron, and passive one receiving signal is postsynaptic neuron.

  22. Classification of Synapses • according toanatomical construction • according tophysiological mechanism • according toeffect of synaptic activity

  23. Anatomical Classification of Synapses • 1) axosomatic synaps (between axson and soma) • 2) axsodendritic synaps (between axson and dendrit) • 3) axoaxonic synaps (between two axons) These are most common, and play role in the transmission of action potentials. • 4) dendrodendritic synaps (between two dendrits) Only in the central nervous system.

  24. Chemical Synapses Electrical Synapses Physiological Classification of SynapsesIn 1930s, there have been various arguments on the synaptic transmission mechanisms between physiologists and pharmacologists. Physiologists put forward that synapses transmitted electrically, whilist pharmacologists considered chemical basis. After improvement in physiological technics, in 1950s and 1960s, it was understood that the underlying mechanism of the synaptic processes is not only a single mechanism; both chemical and electrical activities were effective (Eccles and et al.).

  25. Chemical Synapses During transmission, active neuron releases a chemical substance called neurotransmitter onto the surface of passive neuron. These neurotransmitters including acetylcoline, noradrenaline, dopamine and serotonine are stored in the synaptic vesicles of 300 - 600 Å on the nerve endings of presynaptic terminals.

  26. Chemical transmission occurs in two stages: presynatic and postsynaptic. At presynapticstage, a chemical transmitter is released by presynaptic neuron; postsynaptic procedure covers the effect of the neurotransmitter by receptors of the post synaptic neuron.Postsynaptic mechanism is based on increase or decrease of permeability of the membrane against one or more ion species. Synaptic activities resulting from the increased permeability of the membrane are more common.

  27. There is a narrow gap of 30 nm between pre and post synaptic neurons.Transmission in chemical synapses is slower than that in electrical synapses.

  28. Electrical Synapses In some neurons, e.g. in cerebral cortex, there are no bubbles, and the synaptic gap is bridged by thin fibres. For this reason, electrical synapses are also called bridged synapses. A connection between cytoplasms of pre-synapticand post-synaptic neurons has been established by thin fibers.

  29. The distance between pre and post synaptic terminals is 20 nm (20 Ǻ); this is less than that of chemical synaps by 10 nm. Transmission of electrical synapses, that is very fast, results in synchronized activation of a group of neuron.Electrical synapses are effective in stimulating of extraocular motor neurons which are responsible for stereotypical behaviours such as fast eye movements.

  30. excitatory synapses (depolarization) inhibitory synapses (hyperpolarization) Classification of Synapses According to Synaptic ActivityDepending on the type and effect of the neurotransmitter released by the active neuron during the transmission on passive neuron;

  31. Membrane TrafficIn a neuron, ions (Na, K, Cl, Ca) and organic substances (aminoacids, proteins) are much more than those in sea water and blood. The membrane is semipermeable, because channels are present along the neuron. These channels are called ionic channels.

  32. open channels non-gated channels passive channels provide a pathway for ionic diffussion Closed channels gated channels active channels control of the gate depends on the intensity of physical stimuli at receptor level and effect of neurotransmitters in synaptic terminals. There are two kinds of ionic channels:

  33. Na extracellular fluid intracellular fluid (axoplasm) K open channel gated channel

  34. The behaviour of the channels to ions are selective, but not ideally selective.e.g. a K channel allows 1 Na ion to pass through per 12 K ions.Permeability of the membrane against K and Cl ions is high, but it is low against Na ions. Permeability rates:PK / PNa / PCl ~ 1 / 0.04 / 0.45So, the membrane is 25 times more permeable against K ions compared with that against Na.

  35. The velocity of ions as they pass through the channels are different. Experimental sudies undertaken in the same conditions applying 1 V/cm, showed that movement speed for Na ions was 5 μm/s and 8 μm/s for K. These results were found surprising.Because, Na ions, which are smaller in size, are expected to move faster. These unexpected results were explained based on hydratation factor.The functional sizes of more hydralized Na ions increases; that’s why they move slower.

  36. Active Sodium – Potasium PumpIonic concentrations of the extracellular and intracellular fluids are different. Outside the cell, concentration of Na ions are high, whilist potasiums are more intensive in the inside.So, Na ions tend to diffuse into the cell, as K ions want to go out. This passive diffussion is not out of control.If it was so, the internal and external concentrations of Na and K ions would eventually be in balance, and in the end ionic traffic would stop.Such a result means that biopotentials goes to zero, thus the cell and organism composed of the cells dies.

  37. For the liveliness to continue, various physiological mechanisms, particularly active methabolic Na-K pump, control internal and external concentrations.The action of this pump is in the opposite direction with passive leakage currents.Therefore, the concentrations of Na and K ions are kept at a certain level, by sending excessive ions back.The pump is electrical in character; it sends 3 Na ions back to the outside of the neuron, and 2 K ion back into the neuron.Because passive currents are equal to a few hundred times of the currents carried by the pump, when an impulse is formed, 1 s or more time is necessary for the ionic balance to be restored.

  38. The Resting Membrane PotentialThe difference between internal and external chemical concentrations results in a chemical gradient across the neuron.Because ions are charged, an electrical gradient is also formed.As a result, an electrical potential difference across the membrane occurs, inside the cell being more negative compared with the outside. + 60 – 70 mV -

  39. This potential difference is, in general, called membrane potential.As the neuron is in rest, it is called the resting membrane potential.When the neuron is stimulated by a physical stimuli, it is called depolarized membrane potential.The resting membrane potential is usually around – 90 mV, and it rarely exceeds – 100 mV.

  40. IonicBalanceMathematical analysis of ionic traffic through the membrane has been done to get numerical values for ionic balance. • Nernst equation • Goldman equation

  41. Nernst EquationIn case of ionic balance, the membrane potential defined by Nernst;RT [iyon]o Vm = ------- ln -----------FZ [iyon]iwhere;R: universal gas constant (8.31 j/mol)T: absulate temperature t: temperature of medium in ºCT = 273 + tF: Faraday constant (96500 c/mol)Z: valence value of the ion analysed

  42. If Nernst equation is applied for K ions; 8.31 (273 + t) [K]o Vmk = ------------------- ln -------- 96500 x 1 [K]iat room temperature,t = 37 ºCthe ratio of external and internal concentrations of K ions,[K]o1 -------- = ------ [K]i 20Therefore,8.31 (273 + 37) 1 Vmk = -------------------- ln ----- 96500 x 1 20 Vmk~ - 80 mV

  43. This result means that, if membrane potential is made – 80 mV, K ions will be in balance, and they will not be able to move across the mambrane.This rule is valid in voltage clamp technique which is used for balancing certain ions.So, net potential electrical effect on K ions to prevent their leakage:V*K = Vm – VmkIf the resting membrane potential is accepted to be -60 mV, thenV*K = - 60 – (- 80) = 20 mVThis means that the electrical effect forcing K ions to move across the membrane is to be less than20 mV.

  44. In a biological membrane, theReversal potential (also known as theNernst potential) of an ion is the membrane potential at which there is no net (overall) flow of ions from one side of the membrane to the other. In the case of post-synaptic neurons, the reversal potential is the membrane potential at which a givenneurotransmitter causes no net current flow of ions

  45. Goldman EquationIn Nernst equation; only external and internal chemical concentration differences are considered.Goldman established a more comprehensive equation considering membrane permiabilities against ions in addition to chemical concentration differences; RT PK[K]o + PNa[Na]o + PCl[Cl]i Vm = ------- ln ------------------------------------- F PK[K]i + PNa[Na]i + PCl[Cl]o

  46. If Goldman equation is applied to Na ions, it becomes the same as Nernst equation for any ion of 1 valency; RT [Na]o VmNa~ ------- ln --------- F [Na]iBy placing the relevant numerical values in this equation,8.31 x (273 + 37) 9.1 VmNa~ ----------------------- ln -------- 96500 1 VmNa~ 58 mV

  47. This result means that, if membrane potential is made + 58 mV, Na ions will be in balance, and they will not be able to move across the mambrane.This rule is valid in voltage clamp technic which is used for balancing certain ions.So, net electrical effect on Na ions to prevent their leakage:V*Na = Vm – VNaIf the resting membrane potential is accepted to be -60 mV, then V*Na = - 60 – (58) = - 118 mVThis means that the electrical effect forcing Na ions to move across the membrane is to be less than - 118 mV.

  48. Electrical Parameters of the NeuronThe neuron has four electrical parameters based on its construction and functions: • Voltage source • Current source • Resistance • Capacitance

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