HSF-II Neurophysiology Lecture PDF, 26 Nov 2024

HSF-II: Neurophysiology Lecture Neuronal Transmission & Reflexes Professor Laiche Djouhri, PhD Department of Basic Medical Sciences College of Medicine Email: [email protected]  Objectives By th...

HSF-II: Neurophysiology Lecture Neuronal Transmission & Reflexes Professor Laiche Djouhri, PhD Department of Basic Medical Sciences College of Medicine Email: [email protected]  Objectives By the end of this lecture, you are expected to be able to:  Explain the physiological basis of resting membrane potential  Describe various types of membrane potentials (graded & Chapters 5: Membrane Potential & APs action potentials)  Discuss the ionic mechanisms of action potential (AP)  Describe the steps of synaptic transmission  Define reflex arc and the basic concepts of neural integration Chapters 7: The Nervous System  Definitions-1 extracellular Potential - - to membrane Resting , RMP) -- intracellular -old or Number of positive charges = number of negative charges ❶ Resting membrane potential (RMP): Is a voltage difference between the intracellular and extracellular fluids In other words, it is the electrical force of attraction between positive ions (cations) on outer surface of the membrane and negative ions (anions) on the inner surface of the membrane Principle of bulk electroneutrality All living cells have RMP Depolarization ❷ Depolarization: a change that makes the E ❸ Y #- %, !i s membrane potential less negative than the 4 Repolarization ❶ resting potential. - extracellular ❷ Resting potential #intracellular S ❸ Repolarization: membrane returns to resting ❹ Hyperpolarization potential after depolarization # I extracellulaa  Definitions-2 outD Repolartinis Threshold potential - 70 · After-hyperpolarizationone overshoot ❹ After-hyperpolarization (undershoot): ❻ membrane is more negative than resting state. ❺ Threshold potential: the membrane potential at which action potential (AP) is generated. This is ~ 15 mV less negative than ❼ resting potential ❺ ❻ Overshoot: is part of AP where membrane potential is positive. ❼ Action potential (AP): rapid change in ❹ membrane potential; it is All-or None.  Properties of Cell (Plasma) Membrane  Is an electrically non-conducting thin bilayer (6-8 nm) of phospholipid molecules  2 kinds of important proteins that allow transport of ions through the membrane are built in it: Pumps (e.g. Na+/K+ pump or Na+/K+- ATPase). Ion channels (e.g. Na+ and K+ channels)  The membrane ion channels are of two types: Leak (background) channels: are open all the time Gated channels: have gates which can open & close. Types of Gated Ion Channels Selective Mostly non-selective  Characteristics of Resting Membrane Potential  RMP is the electrical force of attraction between the opposite charges across cell membrane.  Is negative inside relative to outside because of high concentration of negatively charged molecules (inside), such as phosphate, and proteins =  These anions (fixed) cannot diffuse - across the plasma membrane  In mammalian neurons, RMP ranges from- 40 to -75 mV  Ion Concentrations in ECF and ICF  The followings are very important for understanding membrane potential: This table & Na+/K+ pump Leak (background) channels Voltage-gated channels  Na /K + + Pump (Na /K + + ATPase)  This transmembrane protein plays a role in establishing resting membrane - potential -  It moves 3 Na+ ions to outside and 2 K+ ions to inside of cell Extracellular Nat -  It moves Na+ K+ and AGAINST their - concentration gradients & intracellular  It contributes to concentration gradients for Na+ and K+ between ECF and ICF compartments.  Types of Electrical Neuronal Signals They are 2 basic forms of electrical signals: ❷ ❶ Graded potential (GP): is a local electrical AP change in the membrane: ❶GP Occurs in varying grades (can be positive or negative) Its magnitude (size) & duration are directly proportional to strength & duration of the stimulus ❷ Action potential (AP): a short-lasting electrical event that is not dependent on stimulus strength (All-or None)  In neurons, APs play a central role in cell-to-cell communication  APs11/25/2024 serve as long distance signals 10  Types of Graded Potentials They are 2 types of graded potentials that serve as short distance signals: - ❶ Receptor potential & ❷ Postsynaptic potential (excitatory or inhibitory) & ❶ Receptor potential ❷ e.g. skin Postsynaptic potential  : Propagation of Electrical Signals  Electrical signals along neurons are propagated through both passive current flow & active current flow Synaptic Integration: Temporal & Spatial Summation EPSP–IPSP cancellation Temporal summation Spatial summation · EPSP= Excitatory Post-Synaptic Potential - IPSP= Inhibitory g Post-Synaptic Potential  Propagation of Electrical Signals Propagation of Action Potentials Graded potentials Non-selective cation channels  Electrical signals are propagated through flow of both active current and passive current  & Conduction of APs along Nerve Fibers-1  Nerve fibers are either myelinated (A-type) or unmyelinated (C-type)  In A-type fibers APs are only evoked at node of Ranvier  Myelination decreases leak of current  Myelination speeds up AP transmission  Velocity up to 120m/s  Saltatory (jump) conduction Conduction of APs along Nerve Fibers-2 ❶ Saltatory (jump) conduction (Fast) ❷ Continuous conduction (slow) Myelinated fibers Unmyelinated fibers  Ionic Basis of Action Potential-1  AP is caused by conformational (shape) changes in the voltage- gated Na+ and K+ channels ❶  Note that Na+ channels have activation & inactivation gates, but K+ channels have only activation gate  Resting membrane potential (RMP): Both voltage gated Na+ and K+ channels are closed, but membrane is ~ 30 times more permeable to K+ (via leak channels) than Na+.  Resting membrane potential is ~ -70 mV but varies from one neuron to another.  Ionic Basis of Action Potential-2  Initial depolarization:  Some non-selective cation channels open in response to stimulus.  Na+ influx because of the electrochemical driving forces Initial depolarization  The threshold may be reached and an AP is ❷ generated depending on the stimulus strength  Ionic Basis of Action Potential- 3 ❸  Voltage-gated Na+ channels open quickly.  Voltage-gated K+ channels are still closed.  PNa+ > PK+ , (P = permeability)  Ionic Basis of Action Potential- 4 ❹  At the AP peak, Na+ channels self-inactivate  This is followed by opening of voltage-gated K+ channels  This causes repolarization (falling phase)  During this phase PK+ >> PNa+ Depolarization (Na+ Influx) & Repolarization (K+ Efflux) Na+ K+ Depolarization: The membrane suddenly Repolarization: Na+ channels begin to becomes permeable to Na+ ions, allowing close and the K+ channels open. Rapid tremendous numbers of positively diffusion of K+ ions to the exterior re- charged Na+ to diffuse to the interior of establishes the normal negative RMP the cell (upstroke/rising phase).  Ionic Basis of Action Potential-5 Spike/AP ❺  During this phase which is also known as after-hyperpolarization (AHP):  Na+ channels are still inactivated. PK+ at this phase > PK+ at resting state.  Another AP could be generated (relative refractory period) only with strong stimuli.  NO AP could be generated during the absolute refractory period  What Are Neurotransmitters ? Choline ester Amino Acids  Chemical messengers released from pre- synaptic neurons  They excite or inhibit postsynaptic neurons  Synthesized in cytoplasm of cell body and stored in vesicles in axon terminals Neuronal Communication at a Synapse j Chemically gated ion channel (for Na+, EPSP or IPSP is K+, Cl- ) produced Excitatory & Inhibitory Postsynaptic Potentials  Excitatory (EPSP) or inhibitory postsynaptic potentials (IPSP) is produced in postsynaptic membrane  This depends on the type of the NT released & The type of ion channel that opens  An influx of Na+ causes an EPSP ·j  An influx of Cl− (chloride) or - efflux of K+ causes an IPSP - 69  Clinical Significance of Neurotransmitters  Pathophysiology of many neurological disorders has been attributed to changes in neurotransmitters. Examples:  Parkinson’s Disease: dopamine deficiency in the basal nuclei Bite of Black Widow Spider  Alzheimer’s Disease: acetylcholine deficiency  α-latrotoxin: a protein found in the venom of the female black widow spider  Schizophrenia: dopamine excess in the causes : dopaminergic pathway in the brain  An explosive release of  Depression: decreased release of acetylcholine from synaptic vesicles. serotonin or norepinephrine  Respiratory failure due to inability of the diaphragm to relax  What is a Spinal Reflex?  It is a rapid, automatic (involuntary) response to a stimulus (e.g. pinprick)  Reflexes are very important in defending Skin against harmful stimuli & maintaining body support  Reflex arc (reflex circuit) is the pathway followed by nerve impulses that produce a reflex  It includes 5 functional components 27 Example: Withdrawal Reflex (Polysynaptic) Nociceptors = pain receptors Mediated by pain receptors. The response is a reflex contraction of the flexor muscles causing withdrawal of the limb from painful stimulus Amani El Amin