Action Potential PDF 2023

EXCITABLE CELLS AND ACTION POTENTIAL Physiology 2023 H. Yasemin Keskin Ergen  Learning objectives Outline the general features of the excitable cells by comparing with non-excitable cells Explain how the movement of the ions across the membrane leads to a reversibl...

EXCITABLE CELLS AND ACTION POTENTIAL Physiology 2023 H. Yasemin Keskin Ergen  Learning objectives Outline the general features of the excitable cells by comparing with non-excitable cells Explain how the movement of the ions across the membrane leads to a reversible change in the membrane potential Describe the stages of an action potential by naming related ion channels with ionic flows Define absolute and relative refractory periods with underlying reasons  Learning objectives Explain the difference between propagation of action potential in a myelinated and unmyelinated axon Name the factors that are affecting conduction velocity of a neuron Predict the possible effects of the blockage of certain ion channels on generation of action potential  All cells have a “resting” membrane potential as negatively charged on inner face and positively charged on outer face of the membrane (membrane potential).  Excitable cells Examples of excitable cells are neurons, muscle fibers, heart cells, and secretory cells of the pancreas Able to respond several physical effects or chemical messengers by producing reversible changes in the membrane potential These changes in membrane potential is the result of changes in membrane permeability to ions. The excitable cells have gated ion channels, that are responsible for the reversible changes in membrane permeability to ions.  Action Potential An action potential is transient reversal of the transmembrane potential - A rapid rise and subsequent fall in voltage or membrane potential across a cellular membrane with a characteristic pattern 6  A typical neuron has three main region: (from Greek, tree) Receptive & integrative 1- Dendrites portion 2-Cell body (soma) 3-Axon Transmitting portion 7 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006  ACTION POTENTIAL : Rapid change in the membrane potential due to rapid changes in permeability to ions (Na+ and K+ for the neuron). dendrites cell body (soma) axon hillock axon 8 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006  INITIATION OF ACTION POTENTIAL When signals from the dendrites and cell body reach the axon hillock and cause the membrane potential there to become more positive -à depolarization (e.g. from -70 mV to -56 mV ) 9 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006  Approximately 200 years after Luigi Galvani, the electrochemical basis of the nerve action potential was finally elucidated as a phenomenon involving voltage-dependent currents of Na+ and K+ that flow through distinct molecular pathways called Na+ channels and K+ channels. In 1963, Alan L. Hodgkin and Andrew F. Huxley shared the Nobel Prize for their quantitative description of these ionic currents in the squid giant axon in studies involving voltage- clamp recordings. Changes in ionic conductance that underlie the action potential. (Data from Hodgkin AL, Huxley AF: A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500–544, 1952.) Medical Physiology, Third edt. Boron, Walter F., 2017  THRESHOLD If the stimulus that reach the axon hillock is great enough, the neuron depolarizes by about 15 mV and reaches a trigger point, threshold. At the threshold, an action potential is generated. Weak stimuli do not produce an action potential. Action potential (AP) is an all-or-none event. AP always have the same amplitude and same duration Threshold for this neuron is -55mV 12 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006  DEPOLARIZATION At the threshold, This causes more Na+ to flow into depolarization opens the cell, which causes the cell to more voltage-gated Na+ depolarize further and opens channels. more voltage gated Na+ channels. This loop produces the rising phase of the action potential. 13 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006  BEGINING OF REPOLARIZATION The rising phase of the action potential ends when the positive feedback loop is interrupted by: Inactivation of the voltage-gated Na+ channels Opening of the voltage gated K+ channels Voltage-gated Na+ channels are time-sensitive, they close after for a certain period of time. Voltage-gated K channels respond slowly to depolization. They begin to open as the membrane depolarizes, but they respond very slowly. 14 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006  REPOLARIZATION The slow voltage-gated K channels remain open after the cell membrane has repolarized. K+ ions continue to move out of the cell, causing the membrane potential to become more negative than the resting membrane potential. By the end of the hyperpolarization all the K channels are closed. 15 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006 Human Physiology, Cummings 16  All-or-none principle The amplitude of an action potential is independent of the amount of current that produced it. In other words, larger currents do not create larger action potentials. Therefore, action potentials are said to be all-or- none signals, since either they occur fully or they do not occur at all. Greater intensity of stimulation does not produce a stronger signal but can produce a higher frequency of firing. 18  REFRACTORY PERIOD The action potential is followed by a brief period of diminished excitability, or refractoriness, which can be divided into two phases. 1. The absolute refractory: during this period, it is impossible to excite the cell no matter how great a stimulating current is applied. 2. The relative refractory period: during this period, it is possible to trigger an action potential but only by applying stimuli that are stronger than those normally required to reach threshold. These periods of refractoriness, which last just a few milliseconds, are caused by the residual inactivation of Na+ channels and increased opening of K+ channels. 19 REFRACTORY PERIOD The absolute refractory period Many Na+ channels are inactive and will not open, no matter what voltage is applied to membrane The relative refractory period The cell can generate action potential, but only applying stimuli that are stronger than those normally required to reach threshold. Some of the Na+ channels are still inactive and some K+ channels are still open.  Signal conduction Electrical currents in a metal wire are conducted by the flow of electrons, electrical currents across cell membranes are carried by the major ions of body fluid. Axon vs copper wire: Copper wire need not do anything to keep electrical signals moving: it is totally passive, is a good conductor, and is well insulated against losing electrical charge to the outside (electrical signals in copper wires move at about 669 million miles per hour). The axon uses molecular machines (voltage-sensitive ion channels snapping open and closed) to maintain the spike as it travels down its pathway. The saltwater solution on the inside of the axon is not nearly as good a conductor as copper. Moreover, the outer membrane of the axon is a rather leaky insulator.  INFORMATION FLOW IN NEURONS IS DIRECTIONAL Incoming signals are integrated, and if the summed signal is large enough an outgoing signal (AP) is generated at the axon hillock. as action potentials 23 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006 THE ACTION POTENTIAL IS PROPAGATED ALONG THE AXON After the AP is generated at the axon hillock, it is propagated down the axon. Positive charge flows along the axon, depolarizing adjacent areas of the membrane, which reach threshold and generate an AP. AP moves along the axon as a wave of depolarization traveling away from the cell body. Human Physiology: An Integrated Approach 6th edition Dee Unglaub Silverthorn Pearson Physiology by Linda S. Costanzo 5th edt. The voltage response in a passive neuronal process decays with distance due to electronic conduction To be carried successfully to the rest of the nervous system, the local signal must be amplified—it must generate an action potential. 27  Axon MYELINATION Schwann cell (a type of glial cell) wraps Schwann around and around the axon and forms cell myelin sheath. Myelin sheath 28 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006  MYELINATION Neighboring Schwann cells do not touch each other, so there are gaps in the myelin sheath at intervals of 1-2 mm. These gaps (nodes of Ranvier, 2-3 µV) are essential for conduction of the action potential. 29 InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006 SALTATORY CONDUCTION Saltatory (from the Latin saltare, to jump) Action potentials in myelinated nerves are regenerated at the nodes of Ranvier Color Atlas of Neuroscience: Neuroanatomy and Neurophysiology. New York: Thieme,2000. Voltage gated Na+ channels are concentrated at the nodes, thus an AP can be generated only at this region 30  Roles of other ions during the action potential Ca2+ its concentration is more than 10,000 times greater in the ECF than the ICF, There are voltage gated Ca2+ channels contribute to the depolarizing phase on the action potential in some cells. They are often called slow Cardiac muscle cell channels Pacemaker potentials – No stable resting membrane potential – Activity of different types of channels cause graded depolarization of the membrane à If the threshold is reached à action potential – e.g. some neurons, smooth muscle cells, cardiac muscle cells  Conduction velocity Two key parameters influence speed of action potential – The diameter of the axon – The resistance of the axon membrane to ion leakage out of the cell Myelin sheath increase the velocity of nerve transmission approx. 50 fold – Insulates (150-300 membrane layers) – conserves energy Local current loops during action potential propagation. (Medical Physiology, 3rd edt. Boron, Walter F., 2017)  Conduction velocity Change from 0.3 m/sec to 120m/sec (Myelinated large axons) Myelin sheath Axon diameter  Nerve Fiber Types in Mammalian Nerve Ganong's Review of Medical Physiology, 23rd edition  Importance of myelin sheath demyelinating diseases such as multiple sclerosis (an autoimmune disorder in which the myelin sheath surrounding axons is progressively lost) – the propagated action potentials may fail to reach the next node of Ranvier and thus result in nerve blockage – various degrees of paralysis and altered or lost sensation  The importance of membrane potential and action potential Communication, signal transmission Local changes in membrane potential are also used as a signal in some of the non-excitable cells (e.g. hormone secreting endocrine cells) Q - How insulin secreting beta cells in pancreas “know” that blood glucose concentration increased?  What happens if we block the channels that are responsible for the generation of action potential Local anesthetics (e.g. lidocaine) – Block voltage gated Na+ channels – Block sensation Some animals produce toxins (poisons) – e.g. thetrodoxin (TTX, toxin of puffer fish) bind the voltage gated Na+ channels. TTX is produced by certain marine bacteria and is accumulated in some tissues of various invertebrates, amphibians, and fish.  Hodgkin–Huxley model Alan Lloyd Hodgkin and Andrew Huxley (1952) described a model that explain the ionic mechanisms underlying the initiation of action potentials in the squid giant axon. They received the 1963 Nobel Prize in Physiology or Medicine for this work. Hodgkin&Huxley model considers components of cell membrane as an electrical element Diameter of the giant axon @ 0.8 mm  Equivalent circuit The lipid bilayer acts as an insulator between the intracellular and extracellular solutions of conducting ions, and therefore serves as a good capacitor. Voltage-gated channels can be modelled as a conductor (resistor) with an arrow through it. 40  For voltage-gated channels conductance “g” - is a function of both time and voltage For leakage channels conductance is considered as constant By using this model computational neural networks Human Physiology: An Integrated Approach 6th edition Dee Unglaub Silverthorn Pearson  Voltage-gated Ca2+ channels When the action potential reaches Trigger to axon terminal, voltage-gated zone Ca2+ channels open Increase in intracellular Ca2+ concentration triger release of neurtotransmitters 43