HSF-I Neurophysiology.pdf

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 me...

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 & 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 5: Membrane Potential & APs Chapters 7: The Nervous System Definitions-1 ❶ Resting membrane potential (RMP): • Is a voltage difference between the intracellular and extracellular fluids Number of positive charges = number of negative charges • 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 Depolarization ❷ Depolarization: a change that makes the membrane potential less negative than the resting potential. ❸ Repolarization: membrane returns to resting potential after depolarization ❹ After hyperpolarization: membrane is more negative than resting state. Principle of bulk electroneutrality ❸ ❷ Repolarization ❹ ❶ Resting potential After hyperpolarization Definitions-2 overshoot ❺Threshold potential: the membrane potential at which action potential (AP) is generated. This is about 15 mV less negative than resting potential ❻ Overshoot: is part of AP where membrane potential is positive. ❼ Action potential (AP): rapid change in membrane potential; it is All-or None.  Graded potential (GP): is a local electrical change in the membrane that occurs in varying grades (can be positive or negative) ❻ ❼ ❺ 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 What is Resting Membrane Potential?  It is the electrical force of attraction between the opposite charges across the cell membrane.  Is negative inside relative to outside because of high concentration of negatively charged molecules (inside), such as phosphate, and proteins  All living cells have a membrane potential; its value is dependent on cell type  In mammalian neurons, it ranges from40 to -75 mV  These anions (fixed) cannot diffuse across the plasma membrane 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  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  It moves Na+ and K+ AGAINST their concentration gradients  It contributes to concentration gradients for Na+ and K+ between ECF and ICF compartments. + + (Na /K ATPase) Types of Electrical Neuronal Signals They are 2 basic forms of electrical signals: ❶ Graded potential (GP): its magnitude (size) & duration are directly proportional to strength & duration of the stimulus ❷ Action potential (AP): a shortlasting electrical event that is not dependent on stimulus strength (All-or None)  In neurons, APs play a central role in cell-to-cell communication  APs11/17/2023 serve as long distance signals ❷ GP AP ❶ 10 Types of Graded Potentials They are 2 types of graded potentials : ❶ Receptor potential ❷ Postsynaptic potential (excitatory or inhibitory) They are local change in membrane potential that serve as short distance signals e.g. skin Receptor potential ❶ ❷ Postsynaptic potential Synaptic Integration: Temporal & Spatial Summation EPSP–IPSP cancellation Temporal summation Spatial summation EPSP= Excitatory Post-Synaptic Potential IPSP= Inhibitory 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 an Action Potential  Nerve fibers are either myelinated (A-type) or unmyelinated (C-type)  In A-type fibers APs are only evoked at the node of Ranvier  Myelination decreases leak of current  Produces saltatory conduction  Velocity up to 120m/s Myelination Speeds up AP transmission Axon ❶ Saltatory (jump) conduction (Fast) Node of Ranvier ❷ Contiguous (slow) Ionic Basis of Action Potential-1  AP is caused by conformational (shape) changes in the voltagegated 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 a triggering event (e.g., stimulus).  Na+ influx because of the electrochemical driving forces  The threshold may be reached and an AP is generated depending on the triggering event (e.g. the stimulus strength) Initial depolarization ❷ 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 becomes permeable to Na+ ions, allowing tremendous numbers of positively charged Na+ to diffuse to the interior of the cell (upstroke/rising phase). Repolarization: Na+ channels begin to close and the K+ channels open. Rapid diffusion of K+ ions to the exterior reestablishes the normal negative RMP Ionic Basis of Action Potential-5 Spike/AP ❺     During this phase which is also known as afterhyperpolarization (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 Choline ester  Chemical messengers released from presynaptic neurons  They excite or inhibit postsynaptic neurons  Synthesized in cytoplasm of cell body and stored in vesicles in axon terminals Amino Acids What Are Neurotransmitters ? Neuronal Communication at a Synapse EPSP or IPSP is produced Chemically gated ion channel (for Na+, K+, Cl- ) 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  An influx of Cl− (chloride) or efflux of K+ causes an IPSP 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  Alzheimer’s Disease: acetylcholine deficiency  Schizophrenia: dopamine excess in the dopaminergic pathway in the brain  Depression: decreased release of serotonin or norepinephrine Bite of Black Widow Spider  α-latrotoxin: a protein found in the venom of the female black widow spider causes :  An explosive release of acetylcholine from synaptic vesicles.  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 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  25 Skin Example: Withdrawal Reflex (Polysynaptic) Nociceptors = pain receptors Mediated by pain receptors. The response is a reflex contraction of the flexor muscles causing withdrawal Amani El Amin of the limb from painful stimulus