Dr. Amr A. Abd-Elghany

1. Medical Biophysics For Fourth level StudentsTechno. 244 Dr. Amr A. Abd-Elghany

2. Electricity Within the Body • The Nervous System consists of: • I. Central Nervous System. • which consists of: • The Brain. • The Spinal cord. • The Peripheral nerves (neurons). • II. Autonomic Nervous System.

4. Peripheral nervous system Somatic nervous system Autonomic nervous system Sympathetic division Parasympathetic division Enteric division

5. The Central Nervous System • The Brain: • It is surrounded by the protective skull. • It floats in the cerebrospinal fluid (CSF). • It is connected to the spinal cord. • The Spinal Cord: • It is surrounded by the bones of the • vertebral column. • It floats also in the cerebrospinal • fluid (CSF). • The Peripheral nerves (Neurons): • The basic structure unit of the nervous system is the neuron which can be shown as in the following figure;

6. The Central Nervous System • The nerve cell (neuron) is specialized for the, Reception, Interpretation, and Transmission of electrical messages. • The neurons can be classified according to its function to: • Afferent Neurons (Sensory); • Transmit impulse to the brain or spinal cord. • Efferent Neurons (Motor); • Transmit impulse from the brain of spinal cord to the muscles.

7. Basic Tasks of the Nervous System Sensory Input: Monitor both external and internal environments. Integration: Process the information and often integrate it with stored information. Motor output: If necessary, signal effector organs to make an appropriate response.

8. Sensory receptor Sensory neuron Brain LE 28-1b Ganglion Motor neuron Spinal cord Quadriceps muscles Interneuron CNS Nerve Flexor muscles PNS

10. The Central Nervous System • The neurons can be classified according to its structure to: • Myelinated Neuron • The axon of the neuron is covered with a fatty insulating layer called myelin that has small unmyelinated gaps called Nodes of Ranvier. • Unmyelinated Neuron • The axon of the neuron is not covered with myelin sheath Myelinated nerves, which are the most common type in humans, conduct action potential much faster than the unmyelinated nerves.

11. Neurons • Basic structural and functional units of the nervous system. • Cannot divide by mitosis. • Respond to physical and chemical stimuli. • Produce and conduct electrochemical impulses. • Release chemical regulators. • Nerve: • Bundle of axons located outside CNS. • Most composed of both motor and sensory fibers.

12. Neurons are the functional units of nervous systems • Neurons are cells specialized for carrying signals • Cell body: contains most organelles • Dendrites: highly branched extensions that carry signals from other neurons toward the cell body • Axon: long extension that transmits signals to other cells

13. Many axons are enclosed by an insulating myelin sheath • Chain of Schwann cells • Nodes of Ranvier: points where signals can be transmitted • Speeds up signal transmission • Supporting cells (glia) are essential for structural integrity and normal functioning of the nervous system • The axon ends in a cluster of branches • Each branch ends in a synaptic terminal • A synapse is a site of communication between a synaptic terminal and another cell

14. Signal direction Dendrites Cell Body Cell body SEM 3,600 Node of Ranvier Layers of myelin in sheath Signal pathway Axon Schwann cell Nucleus Nucleus Nodes of Ranvier Schwann cell Myelin sheath Synaptic terminals

15. ELECTRICAL POTENTIAL OF NERVES 1. Resting potential -It is the difference in the electrical charges across the membrane in the resting state (without stimulation). -The inside of the cell is more negative than the outside by 60-90mV due to the presence of proteins.

16. Voltmeter Plasma membrane Microelectrode outside cell –70 mV LE 28-3a Microelectrode inside cell Axon Neuron

17. Bioelectric Properties of Neurons Resting Potential • Ion Distribution • Extracellular – NA+ and Cl- • Intracellular – K+ and P-

18. Measurements of Membrane potential The inside of the cell is typically 60 to 90 mV more negative than the outside. This potential difference is called Resting membrane potential

19. What factors contribute to this membrane potential? Sodium-Potassium Pump

20. The Action Potential • It is a large change in the resting potential which • occurs at the point of stimulation and propagates along • the axon. Specifically, the membrane potential goes • from the resting potential (typically -70 mV) to some • positive value (typically about +30 mV) in a very short • period of time (just a few milliseconds) • The action potential is the major method of transmission of • signals within the body. The stimulation may be caused by • various physical and chemical stimuli such as heat, cold, light, • sound and odors.

21. What causes this change in potential to occur?

22. What causes this change in potential to occur?

23. A nerve signal begins as a change in the membrane potential • Electrical changes make up an action potential, a nerve signal that carries information along an axon • Stimulus raises voltage from resting potential to threshold • Action potential is triggered; membrane polarity reverses abruptly • Membrane repolarizes; voltage drops • Voltage undershoots and then returns to resting potential • Cause of electrical changes of an action potential • Movement of K+ and Na+ across the membrane • Controlled by the opening and closing of voltage-gated channels

24. The role of voltage-gated ion channels in the action potential. The circled numbers on the action potential correspond to the four diagrams of voltage-gated sodium and potassium channels in a neuron's plasma membrane (Campbell et al., 1999).

25. +50 Actionpotential 0 Membrane potential (mV) Threshold Threshold –50 Resting potential –100 Time Extracellular fluid Activationgates Potassiumchannel Na+ 1 1 3 2 5 1 4 +  +  +  +  +  +  +  + +  + +  + +  + Plasma membrane –  –  –  –  –  –  –  – –  – –  – –  – Undershoot Cytosol Inactivationgate Sodiumchannel K+ Resting state The role of voltage-gated ion channels in the generation of an action potential(layer 1)

26. +50 Actionpotential Na+ Na+ 0 Membrane potential (mV) Threshold Threshold –50 K+ Resting potential –100 Time Depolarization Extracellular fluid Activationgates Potassiumchannel Na+ 2 1 3 2 5 1 4 1 +  +  +  +  +  +  +  + +  + +  + +  + +  + +  + +  + +  + Plasma membrane –  –  –  –  –  –  –  – –  – –  – –  – –  – –  – –  – –  – Cytosol Inactivationgate Sodiumchannel K+ Resting state The role of voltage-gated ion channels in the generation of an action potential(layer 2)

27. Na+ Na+ K+ Rising phase of the action potential +50 Actionpotential Na+ Na+ 0 Membrane potential (mV) Threshold Threshold –50 K+ Resting potential –100 Time Depolarization Extracellular fluid Activationgates Potassiumchannel Na+ 2 2 5 3 1 4 1 3 1 +  +  +  +  +  +  +  + +  + +  + +  + +  + +  + –  – –  – –  – –  – +  + +  + Plasma membrane –  –  –  –  –  –  –  – +  + +  + +  + +  + –  – –  – –  – –  – –  – –  – –  – Cytosol Inactivationgate Sodiumchannel K+ Resting state The role of voltage-gated ion channels in the generation of an action potential(layer 3)

28. Na+ Na+ Na+ Na+ K+ K+ Falling phase of the action potential Rising phase of the action potential +50 Actionpotential Na+ Na+ 0 Membrane potential (mV) Threshold Threshold –50 K+ Resting potential –100 Time Depolarization Extracellular fluid Activationgates Potassiumchannel Na+ 2 1 4 1 2 3 4 5 1 3 +  +  +  +  +  +  +  + +  + +  + +  + +  + +  + +  + +  + +  + +  + –  – –  – –  – –  – +  + +  + Plasma membrane –  –  –  –  –  –  –  – +  + +  + +  + +  + –  – –  – –  – –  – –  – –  – –  – –  – –  – –  – –  – Cytosol Inactivationgate Sodiumchannel K+ Resting state The role of voltage-gated ion channels in the generation of an action potential(layer 4)

29. Na+ Na+ Na+ Na+ K+ K+ Falling phase of the action potential Rising phase of the action potential +50 Actionpotential Na+ Na+ 0 Membrane potential (mV) Threshold Threshold –50 K+ Resting potential –100 Time Depolarization Na+ Na+ Extracellular fluid Activationgates Potassiumchannel Na+ 4 5 1 1 2 2 4 1 3 5 3 +  +  +  +  +  +  +  + +  + +  + +  + +  + +  + +  + +  + +  + +  + +  + +  + +  + +  + –  – –  – –  – –  – +  + +  + K+ Plasma membrane –  –  –  –  –  –  –  – +  + +  + +  + +  + –  – –  – –  – –  – –  – –  – –  – –  – –  – –  – –  – –  – –  – –  – –  – Undershoot Cytosol Inactivationgate Sodiumchannel K+ Resting state The role of voltage-gated ion channels in the generation of an action potential(layer 5)

30. Na+ K+ Na+ K+ Additional Na+ channels open, K+ channels are closed; interior of cell becomes more positive. LE 28-4-5 Na+ channels close and inactivate. K+ channels open, and K+ rushes out; interior of cell more negative than outside. Na+ +50 Action potential 0 Membrane potential (mV) The K+ channels close relatively slowly, causing a brief undershoot. Na+ Threshold 50 A stimulus opens some Na+ channels; if threshold is reached, action potential is triggered. Resting potential 100 Time (msec) Neuron interior Neuron interior Resting state: voltage-gated Na+ and K+ channels closed; resting potential is maintained. Return to resting state.

31. The Action potential

32. The Nerve Impulse It is a wave that sweeps along the axon which is a sequence of depolarization (entrance of Na+) and Repolarization (exit of K+).

33. Propagation of the Action Potential The action potential is regenerated all along the axon like a series of relay stations. Localized flow of current from the region undergoing an action potential depolarizes the adjacent membrane. Voltage gated Na+ channels in the adjacent membrane respond by opening their activation gates. A new action potential is triggered in the adjacent membrane. This sequence is repeated down the length of the axon. Action potentials don’t decay in strength as they are conducted down the axon.

37. Refractory period Unidirectional Propagation Propagation of the action potential only moves in one direction, from the axon hillock to the axon terminals. The region just recovering from an action potential (K+ outflow region) cannot be stimulated by local current flow. During the repolarizing and undershoot phases, the inactivation gates of the Na+ channels are still closed, blocking any Na+ influx even if the activation gates were to open.

38. Conduction velocity • Impulses typically travel along neurons at a speed of 1 to 120 m/sec. The speed of conduction can be influenced by; • The diameter of a fiber. • The temperature. • The presence or absence of myelin Two primary factors affect the speed of propagation of the action potential; The resistance (R) within the core of the membrane and the capacitance (C) across the membrane.

39. Many vertebrate peripheral neurons have an insulating sheath around the axon called myelin which is formed by Schwann cells. Myelinated Neurons Myelin sheathing allows these neurons to conduct action potentials much faster than in non-myelinated neurons.

40. Saltatory Conduction in Myelinated Axons Myelin sheathing is interrupted by bare patches of axon called nodes of Ranvier where ion channels are concentrated. Action potentials jump from node to node without depolarizing the region under the myelin sheath - called saltatory conduction. Myelin sheathing improves the ability of electrical charge to flow far enough down the axon to reach the next node.

41. Myelinated Neurons Conduct Faster Than Non-myelinated • Action potential • propagates down the axon passively or via • saltatory conduction

42. Factors affect the speed of propagation of the action potential: • The resistance (R) within the core of the membrane • The capacitance (C) (or the charge stored) across the membrane. A decrease in either will increase the propagation velocity

43. Myelinated Neurons Conduct Faster Than Non-myelinated • Myelin sheathing and saltatory conduction improves the speed of nerve impulse conduction. • This allows small diameter neurons to conduct impulses rapidly. • Invertebrates, which don’t have myelinated neurons, have to increase axon diameter to speed up conduction. • The larger the cross-sectional area of a neuron, the further it can conduct electrical charge along the axon.

44. Conduction velocity The depolarization and repolarization process across the axon’s membrane will depend on its time constant; For myelinated axons both the capacitance C and the resistance R are small and thus very short time is needed for the axon to depolarize and repolarize. Accordingly the speed in myelinated neurons is extremely high. On the other hand the non myelinated axons have a high Capacitance and Resistance. Accordingly the time constant will be high, therefore the speed of propagation of the action potential impulse across the non myelinated axon will be small.

45. Conduction velocity Neurons with myelin (myelinated neurons) conduct impulses much faster than those without myelin. The action potentials occur only along the nodes and therefore, impulses jump over the areas of myelin, going from node to node in a process called Saltatory Conduction.

46. Conduction velocity Neurons with myelin (myelinated neurons) conduct impulses much faster than those without myelin. The action potentials occur only along the nodes and therefore, impulses jump over the areas of myelin, going from node to node in a process called Saltatory Conduction.

47. Action potential Waveforms Waveforms of the action potentials from; (a) a Nerve axon (b) a Skeletal muscle cell and (c) a Cardiac muscle cell.

48. Electrical signals from the heart Electrocardiogram (ECG): a device to measure the electrical activity from the heart. Sino-atrial node (SA): a pacemaker which is a special muscle cell located in the right atrium. Atrio-ventricular node (AV):The AV node is an area of specialized tissue between the atria and the ventricles of the heart. It electrically connects atrial and ventricle chambers. Action potential of the heart: when the atrium filled with blood, the SA node now is stimulated. Depolarization occurs after stimulation.

49. Action potential of the heart (Cont.): Contraction occurs a result of depolarization and the blood transfer to the ventricle. Repolarization of the atrium after contraction. The blood passed to the ventricle causes stimulation in the AV node then depolarization, contraction, repolarization and so on. Positions of electrodes (RA, LA, LL): Right arm (RA) and left arm (LA) called lead I. Right arm (RA) and left leg (LL) called lead II. Left leg (LL) and left arm (LA) called lead III.

50. Electrical signals from the heart