Neurophysiology Introduction: Neurons & Action Potentials - Bingham University PDF

NEUROPHYSIOLOGY Dr. Mahan Josiah Mallo Department of Physiology, Bingham University, Karu Physiologic Anatomy of the Neuron  The Neuron Doctrine Neurons are the basic structural and functional unit of the nervous system : Neurons conform to Cell Theory. A cell is the individu...

NEUROPHYSIOLOGY Dr. Mahan Josiah Mallo Department of Physiology, Bingham University, Karu Physiologic Anatomy of the Neuron  The Neuron Doctrine Neurons are the basic structural and functional unit of the nervous system : Neurons conform to Cell Theory. A cell is the individual functional unit of all living organisms The nervous system is made up of the Central NS and the Peripheral NS  Brain Cells The brain is made up of two types of cells: Glia cells and Neuronal cells. Glia cells outnumber the neuronal cells in the ratio of 10:1 Glia cells insulate, support and nourish neurons Neurons process information, sense environmental changes, communicate changes to other neurons and command the body’s responses to environmental stimuli.  Glia (Neuroglia) Smaller than neurons 5 to 50 times more numerous Two types in PNS Schwann cells, myelin forming cells Satellite cells Four types in the CNS Astrocytes Oligodendrocytes, myelin forming cells Microglia Ependymal cells  Neuron Gross Anatomy Neurons are structurally different from other cells in the body. Their unique structure help them to perform their function. - Axon - Cell body or Soma - Dendrites - Synaptic terminals February 20, 2025 Cell Structure of Neurons February 20, 2025  Neuron Classification Neurons can be classified according to Structural Classification: number of processes (axons and dendrites) that extend from the soma Unipolar: a neuron that has a single neurite Bipolar: a neuron that has two neurite one axon, Multipolar: a neuron that has three or more neurite Function Sensory neurons carry messages toward brain Motor neurons carry messages from brain to muscles and glands Interneurons connect neuronal cells Neurotransmitter released by neuron Effects of neurotransmitter (excitatory vs. inhibitory) February 20, 2025  Functional Classification of Neurons Neurons can be divided into three functional classes 1. Afferent neurons: (A) Transmits information into the CNS from receptors at their peripheral endings (B) Single process from the cell body splits into a long peripheral process (axon) that is in the PNS and a short central process (axon) that enters the CNS 2. Efferent neurons: (A) Transmits information out of the CNS to effector cells, particularly muscles, glands, neurons and other cells (B) Cell body with multiply dendrites and a small segment of the axon are in the CNS, most of the axon is in the PNS February 20, 2025  Functional Classification of Neurons… 3. Interneurons: (A) Function as integrators and signal changers (B) Integrate groups of afferent and efferent neurons into reflex circuits (C) Lie entirely within the CNS (D) Account for about 90% of all neurons. The number of interneurons interposed between specific afferent and efferent neurons varies according to the complexity of the action they control. The knee-jerk reflex elicited by tapping below the kneecap activates thigh muscles without interneurons, the afferent neurons interact directly with efferent neurons. February 20, 2025 February 20, 2025  Functional Classification of Neurons… In contrast, when you hear a song or smell a certain perfume that evokes memories of someone you know, millions of interneurons may be involved. February 20, 2025  Terms to Know Voltage (V): It is the measure of potential energy between two points generated by a charge separation Potential or Potential difference: It is the voltage difference between two points Membrane Potential: It is the voltage difference between the inside and outside of a cell Resting membrane potential: It is the steady transmembrane potential of a cell that is not producing an electrical signal. In neurons it is about - 70mV. February 20, 2025 Resting Membrane Potential All cells under resting conditions have a potential difference across their plasma membranes, with the inside of the cell negatively charged with respect to the outside. The RMP exists because of a tiny excess of –ve ions inside the cell and an excess of +ve ions outside. 80% caused by selective permeability of the cell membrane to Kᶧ. The Kᶧ diffuses out of the cell according to concentration gradient 20% is caused by the Naᶧ/Kᶧ pump Resting Membrane Potential Definition: it is the potential difference recorded across the cell membrane at rest. Causes: 80% caused by selective permeability of the cell membrane to K+ The K+ diffuses out of the cell & Na+ diffuses into the cell according to concentration gradient. The K+ permeability is 50-75 folds more than Na+ 20% is caused by the Na+ K+ pump an active process that needs energy taken from ATP. This is very important to maintain the concentration gradient across the cell membrane  Equilibrium Potential In a cell that is permeable to only one ion, the membrane potential that exactly opposes the concentration of the ion is known as the equilibrium potential. Eion = ENa, ECl, EK. So the Potassium EP or EK is the membrane potential at which the chemical and electrical gradients are equal in magnitude and opposite in direction, resulting in no net movement of Kᶧ It is calculated using the Nernst or Goldman equation Naᶧ EP is +60mV, while that of Kᶧ is -90mV. February 20, 2025 Nernst Equation Use to calculate the membrane potential of an ion at equilibrium Represents the electrical potential necessary to maintain a certain concentration gradient of a permeable solute Z is valence of the ion  Goldman’s Equation Em (60mv)log P K   P Na  P Cl  k o Na o Cl i P K   P Na  P Cl  k i Na i Cl o Used to calculate overall membrane potential when multiple ions are involved. Incorporates permeability of each ion. Permeability of K+ > Na+ > Cl- … thus.. K+ drives Resting Membrane Potential  Electrical Signals in Neurons All living cells have a RMP due to the presence of ion pumps and leak channels in the cell membrane. This difference in charge can be measured as potential energy- measured in millivolts. In addition, however, some cells have another group of ion channels that can be gated (opened or closed) under certain conditions. Such channels give a cell the ability to produce electrical signals that can transmit information between different regions of the membrane. This property is known as Excitability and such membranes are called excitable membranes February 20, 2025  Electrical Signals in Neurons Cells of this type includes all neurons and muscle cells, as well as some endocrine, immune and reproductive cells. The electrical signals occur in two forms: graded potentials and action potentials. GP are important in signaling over short distances, whereas AP are long-distance signals that are particularly important in neuronal and muscle cell membranes. February 20, 2025  Terms to Know The terms depolarize, repolarize and hyperpolarize are used to describe the direction of changes in the membrane potential. Changes in membrane potential act as electrical signals. The RMP is “polarized”, which simple means that the outside and inside of a cell have a different net charge. The membrane is depolarized when its potential becomes less –ve (closer to zero) than the resting level February 20, 2025  Terms to Know Overshoot refers to a reversal of the membrane potential polarity, that is when the inside of a cell becomes positive relative to the outside. When a membrane potential that has been depolarized is returning toward the resting value, it is repolarizing. The membrane is hyperpolarized when the potential is more –ve than the resting level. February 20, 2025 February 20, 2025  Graded Potential GP in neurons are depolarizations or hyper polarizations that occur in the dendrites and cell body or, less frequently, near the axon terminals. These changes in membrane potential are called “graded” because their size, or amplitude is directly proportional to the strength of the triggering event. A large stimulus will cause a strong graded potential, and a small stimulus will result in a weak graded potential. February 20, 2025  Graded Potential So GP is a potential change of variable amplitude and duration that is conducted decrementally, they usually die out in 1-2mm of the origin. It has no threshold and refractory period. GPs are given various names related to the location of the potential or the function they perform, for instance, receptor potential, synaptic potential and pacemaker potential are all different types of GPs. February 20, 2025 February 20, 2025 February 20, 2025  Action Potential An AP is a regenerating depolarization of membrane potential that propagates along an excitable tissue. The threshold of most excitable membranes is about 15mV less negative than the RMP. Thus, if the resting membrane potential of a neuron is -70mV, the threshold potential may be -55mV. February 20, 2025 February 20, 2025  Action Potential Con’t 1. Steady resting potential is near Ek, Ek > ENa, due to Kᶧ channels. 2. Local membrane is brought to threshold voltage by depolarizing stimulus. 3. Current through opening voltage-gated Naᶧ channels rapidly depolarizes the membrane, causing more Naᶧ channels to open. 4. Inactivation of Naᶧ channels and delayed opening of voltage-gated Kᶧ channels halt membrane depolarization. February 20, 2025  Action Potential Con’t 5. Outward current through open voltage-gated Kᶧ channels repolarizes the membrane back to a -ve potential. 6. Persistent current through slowly closing voltage-gated K channels hyperpolarizes membrane toward Ek; Na channels return from inactivated state to closed state (without opening). 7. Closure of voltage-gated K channels returns the membrane potential to its resting value. February 20, 2025  Voltage-Gated Channels Change shape due to changes in membrane potential Closed at resting potential Positive feedback Influx of Na+  local depolarization  more Na+ channels open  more depolarization Na+ channels open first (depolarization) K+ channels open more slowly (repolarization) Na+ channels close K+ channels close slowly relative refractory period caused by open K+ channels February 20, 2025 Action Potential Con’t February 20, 2025 February 20, 2025 February 20, 2025 February 20, 2025  Characteristics of AP Action potentials Need to reach threshold Are all-or-none events Have constant amplitude Do not summate Are initiated by depolarization Involve changes in permeability Rely on voltage-gated ion channels February 20, 2025  Applications Local anesthetics are drugs that temporarily block action potentials in axons. They are called Local because they are injected directly into the tissue where anesthesia (the absence of sensation) is desired  Action Potential Con’t The generation of APs is prevented by local anesthetics such as procaine and lidocaine, because these drugs block voltage-gated Na+ channels, preventing them from opening in response to depolarization. Without AP graded signals generated in sensory neurons in response to injury, for example cannot reach the brain and give rise to the sensation of pain. February 20, 2025  Action Potential Con’t Some animals produce toxins (poisons) that work by interfering with nerve conduction in the same way that local anesthetics do. For example, some organs of the pufferfish produce an extremely potent toxin, tetrodotoxin, that binds to voltage-gated Na+ channels and prevents the Na+ component of the AP February 20, 2025  Absolute Refractory Periods During the AP, a second stimulus, no matter how strong, will not produce a second AP. That region of the membrane is then said to be in its absolute refractory period. The absolute refractory period represents the time required for the Naᶧ channel gates to reset to their resting positions. The ARP ensures that a second AP will not occur before the first has finished. AP cannot overlap and cannot travel backward because of their refractory periods. February 20, 2025  Relative Refractory Period A relative refractory period follows the absolute refractory period. A stronger than normal depolarizing graded potential is needed to bring the cell up to threshold, and the AP will be smaller than normal February 20, 2025  Uses of Refractory Periods The refractory periods limit the number of AP an excitable membrane can produce in a given period of time. Most neurons respond at frequencies of up to 100 APs per second, and some may produce much higher frequencies for brief periods. RPs contribute to the separation of these APs so that individual electrical signals pass down the axon. The RPs also are the key in determining the direction of AP propagation. February 20, 2025 Functions of Action Potentials i. Information delivery to CNS : carriage of all sensory input to CNS. ii. Information encoding :The frequency of APs encodes information February 20, 2025 Functions of Action Potentials iii. Rapid transmission over distance (nerve cell APs) Note: speed of transmission depends on fiber size and whether it is myelinated. Information of lesser importance carried by slowly conducting unmyelinated fibers. iv. In non-nervous tissue APs are the initiators of a range of cellular responses muscle contraction secretion (eg. Adrenalin from chromaffin cells of medulla) February 20, 2025  Conduction Speed The velocity with which an AP propagates along a membrane depends upon fiber diameter and whether or not the fiber is myelinated. The larger the fiber diameter the faster the AP propagates. This is because a large fiber offers less internal resistance to local current More ions will flow in a given time, bringing adjacent regions of the membrane to threshold February 20, 2025 February 20, 2025 February 20, 2025 February 20, 2025 February 20, 2025 February 20, 2025 February 20, 2025  Effect of Myelin on Conduction Velocity The two neurons illustrated below would have equal conduction velocities. 6 mm diameter myelinated 500 mm diameter unmyelinated  Uses of Myelin Conduction velocity is increased Size requirement is diminished Electrical insulation Reduced cell-energy requirement February 20, 2025