MED201-L-3 - Propagation of Action Potential.pdf

Propagation of Action Potentials Instructors : Dr. Talay Yar email: [email protected] Dr. Mona AlSheikh email: [email protected] Department of Physiology Thursday, November 2, 2023 10:21 Learning Objectives After participating successfully in this session students should understand:  that, fro...

Propagation of Action Potentials Instructors : Dr. Talay Yar email: [email protected] Dr. Mona AlSheikh email: [email protected] Department of Physiology Thursday, November 2, 2023 10:21 Learning Objectives After participating successfully in this session students should understand:  that, from a site on the nerve cell membrane that is producing an AP, current can flow electrotonically (passively) to areas of the neuron that are still at rest  electrotonic flow of current does not travel far down the neuron (the neuron is a leaky structure the current leaks out), → information about the event that elicited the AP may not travel far  problem is overcome in neurons : electrotonic current flow → depolarise adjacent resting regions of the neuron to threshold → AP at these regions, and that this “refreshes” the message through “fresh” current flow  flow of current and the production of new APs is rapid so that the transmission of APs is like a wave of depolarisation spreading along the neuron from the initial site,  this transmission of APs only goes in one direction under normal circumstances  continual regeneration of APs is an event that slows the flow of information down the neuron  two mechanisms to speed up such transmission (i.e., speed up the conduction velocity of information) and why each of these two mechanisms increases the conduction velocity  These mechanisms form the basis for scheme for classification of nerve fibers  dysfunctions of myelination can cause disruption of the transmission of information in normally-myelinated neurons Thursday, November 2, 2023 Propagation of Action Potential 2 10:21 Self assessment ▪ What are the differences between the two types of electrical signaling in the body, i.e., the graded potential and the action potential Property GP AP Trigger Stimulus, ntr, GP to threshold Ion Na, K, Cl , Ca Sequential Na, K movement - VG ch Magnitude Proportional to stimulus All or none Duration Proportional Constant Spread Decremental Throughout Refractory Period None Relative, absolute Summation Temporal, spatial none Location RP,PSP, Cell body, axon, terminal Direction of potential change depolarization, depolarization hyperpolarization Thursday, November 2, 2023 Propagation of Action Potential 10:21 Case Scenario ▪ Nadia, a 27 years old nurse, started having tingling and numbness sensations in hands and feet for the last few weeks but she did not take it seriously She observed of having muscle weakness and fatigue during the ward round, due to which she had to discontinue the ward round several times. One day she was not able to maintain her balance and coordination and fell down while taking the blood pressure of a patient. She discussed her condition with the duty doctor, who advised her to consult a neurologist. The neurologist advised her to undergo electrophysiological studies which revealed that the speed of conduction of impulses along her motor nerves was slower than expected. On the basis of history and investigations, a provisional diagnosis of multiple sclerosis was made. Thursday, November 2, 2023 Propagation of Action Potential 10:21 Propagation of action potential occurs along nerve fibers by Saltatory Conduction my at at nodes of Ranvier Contiguous Conduction by local current flow Thursday, November 2, 2023 Propagation of Action Potential 10:21 if Input Zone Dendrites and I What do cells require to develop action potential? Cell body starts Nucleus potential Action How is action potential propagated Trigger Zone Axon hillock Axon Hillock have abundance of voltage gated sodium channels, which help to achieve threshhold. Conducting Zone Axon (may be from 1mm Once threshold potential is achieved an action potential is generated at axon Hillock and transmitted through the conducting Zone. Thursday, November 2, 2023 to more than 1m long) Propagation of Action Potential Output Zone Axon terminals Uneven Distribution of ion Channels in nerve cells ▪ Voltage gated Na+ channels (VGNa ch) a prerequisite for AP generation. ▪ VG Na+ ch are present in abundance in the Axon especially at • • • nodes of Ranvier and axon hillock – axon hillock- trigger zone –the site of generation of the first AP nerve terminals. i In myelinated axons: As no AP is generated in the myelinated areas so no need of having VGNa ch under the myelin. – Also present in the cell body and dendrites but relatively less. ▪ VG K+ channels are present alongside VG Na channels as they have an important role in repolarization phase of AP. ▪ VG Ca++ channels: in the nerve terminal (Ca influx for initiating release of neurotransmitter from the presynaptic terminal). as is t.dkbadat Neurotransmitter Thursday, November 2, 2023 7 L 10:21 Active area at peak of action potential Adjacent inactive area into which depolarization is spreading; will soon reach threshold Remainder of axon still at resting potential Local current flow that depolarizes adjacent inactive area from resting to threshold Direction of propagation of action potential 1 Contiguous Conduction by local current flow Thursday, November 2, 2023 Propagation of Action Potential 10:21 Active area at peak of action potential Adjacent inactive area into which depolarization is spreading; will soon reach threshold Remainder of axon still at resting potential Local current flow that depolarizes adjacent inactive area from resting to threshold Direction of propagation of action potential Contiguous Conduction Thursday, November 2, 2023 Propagation of Action Potential Previous active area returned to resting potential 1 Adjacent area that was brought to threshold by local current flow; now active at peak of action potential 2 New adjacent inactive area into which depolarization is spreading; will soon reach threshold 3 10:21 Remainder of axon still at resting potential 4 Contiguous Conduction by local current flow Thursday, November 2, 2023 Propagation of Action Potential 10:21 Contiguous Conduction ▪ Action potentials do not flow by a passive current flow, instead they are regenerated at every new point. ▪ Each new action potential is a fresh new event that depends on the induced permeability changes and electrochemical gradients that are identical down the length of the axon. Thursday, November 2, 2023 Propagation of Action Potential 10:21 Contiguous Conduction Once action potential is initiated in one part of the neuron, a self-perpetuating cycle is initiated so that the AP is propagated along the rest of the fiber automatically. Thursday, November 2, 2023 Propagation of Action Potential 10:21 Graded potentials spread by passive current flow, i.e., the same sodium ions which entered the membrane by the initial stimulus are moving passively along the membrane. New action potentials are not generated (in case of graded potentials) at each point because of too few number of voltage gated sodium channels in these membranes Difference between the transmission of graded and action potentials Thursday, November 2, 2023 Propagation of Action Potential 10:21 Saltatory conduction (Jumping action potentials) • Occurs in myelinated nerve fibers dis S ✓ The Schwann cell forms myelin in the peripheral nervous spinalcordsi spiralloud is 2st may system and oligodendrocytes in the central nervous system ✓ The unmyelinated areas are called as nodes of Ranvier Thursday, November 2, 2023 Propagation of Action Potential Saltatory Conduction Occurs at nodes of Ranvier Nodes of Ranvier The unmyelinated areas are called as nodes of Ranvier 1mm Myelin Axon Thursday, November 2, 2023 Propagation of Action Potential 10:21 Myelin and the Nodes of Ranvier Schwann cell in peripheral nervous system Oligodendroglia in central nervous system Thursday, November 2, 2023 Propagation of Action Potential 16 10:21 Saltatory Conduction Occurs Schwann cell coverd by Mylein sheath at nodes of Ranvier Node of Ranvier Saltatory conduction Thursday, November 2, 2023 Propagation of Action Potential 10:21 Active node at peak of action potential Adjacent inactive node into which depolarization is spreading; will soon reach threshold Remainder of nodes still at resting potential Myelin Local current flow that depolarizes adjacent inactive node from resting to threshold Direction of propagation of action potential Thursday, November 2, 2023 Propagation of Action Potential Myelinated axon 10:21 Previous active node returned to resting potential Thursday, November 2, 2023 Adjacent node that was brought to threshold by local current flow; now active at peak of action potential Propagation of Action Potential New adjacent inactive node into which depolarization is spreading; will soon reach threshold Refractory period at the area where the foot is pressing on the pipe to send the wave forwards→ Thursday, November 2, 2023 10:21 Factors affecting the speed of conduction of the impulse. ▪ The strength of the stimulus is coded by frequency of action potentials. ▪ BUT ▪ The speed of conduction depends on – Myelination of the fiber (if the fiber is myelinated…speed of conduction is fast). – Diameter of the fiber (if the diameter of fiber is more …the impulse moves faster). Thursday, November 2, 2023 Propagation of Action Potential Conduction velocity - non-myelinated vs myelinated - non-myelinated myelinated Thursday, November 2, 2023 The two mechanisms that speed up impulse transmission (conduction velocity) form the basis for scheme for classification of nerve fibers ▪ Nerve fibers are classified according to axon diameter and presence of myelination. Thursday, November 2, 2023 Thursday, November 2, 2023 10:21 Some Examples of Demyelination disease Disaster! • Guillain-Barré syndrome (GBS) • Multiple sclerosis • Dementias (white matter degeneration) GBS: muscle weakness caused by the immune system damaging the peripheral nervous system (loss of myelin insulation). Rapid onset. 2/100000 Thursday, November 2, 2023 Propagation of Action Potential 25 Dementia: An overall term for diseases and conditions characterized by a decline in memory, language, problem-solving and other thinking skills that affect a person's ability to perform everyday activities. ▪ Alzheimer's is the most common cause of dementia. ▪ Degenerative disease of cortex ▪ Slow onset memory loss (first short term memory and progresses to long term memory), and progressive disorientation. Thursday, November 2, 2023 Multiple Sclerosis: multiple lesions in time & space Immune-mediated inflammatory demyelinating disease of the CNS 1 person/per 1000 in US female-to-male ratio is 2:1 - May present with paresthesias of a hand that resolves, followed in a couple of months by weakness in a leg or visual disturbances. Patients frequently do not bring these complaints to their doctors because they resolve. Eventually, the resolution of the neurologic deficits is incomplete or their occurrence is too frequent. http://www.emedicine.com/pmr/topic82.htm Thursday, November 2, 2023 Thursday, November 2, 2023 10:21 1. SELF ASSESSMENT 27 years old Nadia, A nurse by profession started having tingling and numbness sensations in hands and feet for the last few weeks but she did not take it seriously She observed of having muscle weakness and fatigue during the ward round, due to which she had to discontinue the ward round several times. One day she was not able to maintain her balance and coordination and fell down while taking the blood pressure of a patient. She discussed her condition with the duty doctor, who advised him to consult a neurologist. Neurologist advised her to undergo electrophysiological studies which revealed that the speed of conduction of impulses along her motor nerves was lower than expected. On the basis of history and investigations, a diagnosis of multiple sclerosis was made. What can be the physiological basis of decreased speed of conduction of impulse in this patient. How can you correlate her signs and symptoms with the decreased speed of impulse conduction. What are the factors which have an effect on the speed of conduction of impulses? Enumerate some conditions causing the demyelination of the nerves. Thursday, November 2, 2023 Propagation of Action Potential 10:21 Self assessment ▪ What are the differences between the two types of electrical signaling in the body, i.e., the graded potential and the action potential Property GP AP Trigger Stimulus, ntr, GP to threshold Ion Na, K, Cl , Ca Sequential Na, K movement - VG ch Magnitude Proportional to stimulus All or none Duration Proportional Constant Spread Decremental Throughout Refractory Period None Relative, absolute Summation Temporal, spatial none Location RP,PSP, Cell body, axon, terminal Direction of potential change depolarization, depolarization hyperpolarization Thursday, November 2, 2023 Propagation of Action Potential 10:21 Sherwood Physiology 8th edition. Chapter 4, Page numbers 96 to 111, Sherwood Physiology, 7th edition, Chapter 4, Page numbers 87 to 103 Guyton and Hall Textbook of Medical Physiology, 13th ed, Chapter 5, pages 61-67 Thursday, November 2, 2023 Propagation of Action Potential 10:21 Thursday, November 2, 2023 Propagation of Action Potential 10:21 Functional Parts of a Neuron Receptor zone or Input Zone Release zone or Output Zone Axon terminals Receptor zone or Input Zone Dendrites and Cell body Trigger Zone Axon hillock Conducting Zone Axon Thursday, November 2, 2023 Generation of Action Potential