Topic 2: Cellular Physiology of Nerve and Muscle (Part 1) Required Readings: • Plasma Membrane: Chapter 3: p. 63-81 • Neurons: Chapter 11: p.394 (neurons) – 397 (myelination); p. 400 – 420 • Muscle: Chapter 9: p. 279 - 314 Université d’Ottawa | University of Ottawa Disclosure You may only access and use this PowerPoint presentation for educational purposes. You may not post this presentation online or distribute it without the permission of the author. uottawa.ca Objectives Part I Membrane Transport 2.1.1. Describe the structure of the plasma membrane 2.1.2. Describe and differentiate among the various types of transport across the plasma membrane 2.1.3. Describe osmosis and explain its role in fluid homeostasis Neurons 2.2.1 Identify the different regions of the neuron and associate each region with the functions of reception, propagation and transmission of nerve impulses 2.2.2.Explain the phenomena (diffusion of ions, types of ion channels) that are responsible for the electrical activity of neurons (resting membrane potential, action potential) 2.2.3 Describe the factors that influence propagation of the action potential along an axon 2.2.4 Explain the mechanisms of synaptic transmission (synapse, post-synaptic potentials, synaptic integration) PLASMA MEMBRANE • Also known as the “cell membrane” • acts as an active barrier separating intracellular fluid (ICF) from extracellular fluid (ECF) • selectively permeable /plays role in cellular activity by controlling what enters and what leaves cell • allows the cell to respond to changes in the extracellular fluid • communication: site of cell-to-cell interaction and recognition PLASMA MEMBRANE Basic structure according to fluid mosaic model: • phospholipid bilayer • Membrane proteins • Surface sugars form glycocalyx • Membrane structures help to hold cells together through cell junctions PLASMA MEMBRANE • Lipid bilayer – 75% phospholipids, which consist of two parts: Phosphate heads: are polar (charged), so are hydrophilic (water-loving) Fatty acid tails: are nonpolar (no charge), so are hydrophobic (water-hating) – 5% glycolipids Lipids with sugar groups on outer membrane surface – 20% cholesterol Increases membrane stability PLASMA MEMBRANE Membrane Proteins • Make up about half the mass of plasma membrane • Allow cell communication with environment • Most have specialized membrane functions • Some float freely, and some are tethered to intracellular structures PLASMA MEMBRANE Two types Integral proteins • Firmly inserted into membrane • Most are transmembrane proteins (span membrane) • Have both hydrophobic and hydrophilic regions Function as transport proteins (channels and carriers), enzymes, or receptors Peripheral Proteins • Loosely attached to integral proteins • Include filaments on intracellular surface used for plasma membrane support Function as: o Enzymes o Motor proteins for shape change during cell division and muscle contraction o Cell-to-cell connections Functions of Plasma Membrane Proteins (a)Transport A protein (left) that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. Some transport proteins (right) hydrolyze ATP as an energy source to actively pump substances across the membrane. (b) Receptors for signal transduction A membrane protein exposed to the outside of the cell may have a binding site that fits the shape of a specific chemical messenger, such as a hormone. When bound, the chemical messenger may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell. (c) Enzymatic activity A membrane protein may be an enzyme with its active site exposed to substances in the adjacent solution. A team of several enzymes in a membrane may catalyze sequential steps of a metabolic pathway as indicated (left to right) here. Functions of Plasma Membrane Proteins (d) Cell-cell recognition Some glycoproteins (proteins bonded to short chains of sugars which help to make up the glycocalyx) serve as identification tags that are specifically recognized by other cells. (e) Attachment to the cytoskeleton and extracellular matrix (ECM) Elements of the cytoskeleton (cell’s internal framework) and the extracellular matrix (fibers and other substances outside the cell) may anchor to membrane proteins. Helps maintain cell shape, fixes the location of certain membrane proteins, and plays a role in cell movement. (f) Cell-to-cell joining Membrane proteins of adjacent cells may be hooked together in various kinds of intercellular junctions. Some membrane proteins (cell adhesion molecules or CAMs) of this group provide temporary binding sites that guide cell migration and other cell-to-cell interactions. PLASMA MEMBRANE Membrane Carbohydrates and Glycocalyx • Consists of sugars (carbohydrates) sticking out of cell surface – Some sugars are attached to lipids (glycolipids) and some to proteins (glycoproteins) • Every cell type has different patterns of this “sugar coating” – Functions as specific biological markers for cellto-cell recognition – Allows immune system to recognize “self” vs. “nonself” Cell Junctions MEMBRANE TRANSPORT • Substances must constantly move across the plasma membrane – Some molecules pass through easily; some do not • Plasma membrane is selectively permeable allowing only certain molecules to cross • Two essential ways substances cross plasma membrane: – Passive transport: no energy is required – Active transport: energy (ATP) is required Passive Transport Three types of passive transport Simple Diffusion Facilitated diffusion Osmosis • All types involve diffusion – natural movement of molecules from areas of high concentration to areas of low concentration • Also referred to as moving down a concentration gradient GRADIENTS Concentration gradient Electrical gradient Passive Transport Diffusion • Movement down a concentration gradient. What is a gradient? • Molecules in higher concentration areas collide more resulting in molecules being scattered to lower concentration areas Speed of diffusion influenced by 3 factors: – Concentration: the steeper the gradient, the faster diffusion occurs – Molecular Size: smaller molecules diffuse faster – Temperature: higher temps increase kinetic energy which results in faster diffusion Equilibrium is reached when there is no net movement of molecules in one direction only What determines whether a substance can cross the plasma membrane? Lipid-soluble and nonpolar substances Size: Very small molecules that can pass through membrane or membrane channels Passive Transport Simple Diffusion • Nonpolar, lipid-soluble (hydrophobic) substances diffuse directly through phospholipid bilayer e.g., O2, CO2, steroid hormones, fatty acids • Small amounts of very small polar substances, such as water, can even pass Facilitated Diffusion Larger or non-lipid soluble or polar molecules can cross membrane but only with assistance of carrier molecules Referred to as facilitated diffusion Certain hydrophilic molecules (e.g., glucose, amino acids, and ions) are transported passively down their concentration gradient by: • Carrier-mediated facilitated diffusion – Substances bind to protein carriers • Channel-mediated facilitated diffusion – Substances move through water-filled channels Passive Transport Facilitated Diffusion A.Carrier-Mediated • lipid-insoluble molecules too large to pass through membrane pores/channels • Carriers are transmembrane integral proteins Features of carrier mediated diffusion: 1. specific 2. not ATP-requiring 3. limited by carrier saturation. What is the transport maximum? 4. movement down concentration gradient 5. can be inhibited by certain substances What is the most well-known substance that is transported by carrier-mediated facilitated diffusion? Passive Transport Facilitated Diffusion B. Channel-Mediated • Channels with aqueous-filled cores are formed by transmembrane proteins • Channels transport molecules such as ions or water (osmosis) down their concentration gradient • selective due to pore size, charge of a.a. that line channels • Water channels are called aquaporins Two types: • Leakage channels: are always open • Gated channels: opening is controlled by chemical or electrical signals Note: • Movement always down concentration gradient • Can be inhibited, can show saturation & are usually specific Osmosis – Special name for movement of solvent (not molecules), such as water, across a selectively permeable membrane – Water diffuses across plasma membranes • through lipid bilayer (even though water is polar, it is so small that some molecules can sneak past nonpolar phospholipid tails) • through specific water channels called aquaporins (AQPs) – Flow occurs when water (or other solvent) concentration is different on the two sides of a membrane Osmosis Osmolarity: measures the concentration of the total number of solute particles in solvent Does a solution of 1 M NaCl have the same osmolarity as a solution on 1 M MgCl2? solutions of different osmolarities separated by a membrane permeable to all molecules: • diffusion of solutes & osmosis of H2O occur across membrane equilibrium of solutes & H2O is reached Solutions of different osmolarities separated by a membrane permeable only H2O • only osmosis (not diffusion) will occur until equilibrium is reached Osmosis Movement of water involves pressures: – Hydrostatic pressure: outward pressure exerted on cell side of membrane caused by increases in volume of cell due to osmosis Also referred to as “back pressure” – Osmotic pressure: inward pressure due to tendency of water to be “pulled” into a cell with higher osmolarities The more solutes inside a cell the bigger the pull on water to enter, resulting in higher osmotic pressures inside the cell http://upload.wikimedia.org/wikipedia/commons/ 0/03/Illu_capillary_microcirculation.jpg Osmosis Tonicity Ability of a solution to change the shape or tone of cells by altering the cells’ internal water volume • Isotonic solution has same osmolarity as inside the cell, so volume remains unchanged • Hypertonic solution has higher osmolarity than inside cell, so water flows out of cell, resulting in cell shrinking – Shrinking is referred to as crenation • Hypotonic solution has lower osmolarity than inside cell, so water flows into cell, resulting in cell swelling – Can lead to cell bursting, referred to as lysing The effect of solutions of varying tonicities on living red blood cells Active Transport Two major active membrane transport processes • Primary & Secondary Like facilitated diffusion both require carrier proteins (solute pumps): combines specifically & reversibly with substance unlike facilitated diffusion, solute pumps move substances (amino acids, Na+, K+, Ca+) AGAINST CONCENTRATION GRADIENTS https://i.ytimg.com/vi/WgmJ8NKLgAg/maxresdefault.jpg Active Transport 1. Primary Active Transport • Requires energy directly from ATP hydrolysis – Energy from hydrolysis of ATP causes change in shape of transport protein – Shape change causes solutes (ions) bound to protein to be pumped across membrane + + – Example of pumps: calcium, hydrogen (proton), 𝑁𝑎 −𝐾 pumps Most studied is the Na+-K+ pump – An enzyme, called Na+-K+ ATPase, that pumps Na+ out of cell and K+ back into cell – Located in all plasma membranes, but especially active in excitable cells (nerves and muscles) • • [K+] 10-20X higher inside cell than out; [Na+] higher outside cell gradients essential to maintain normal cell function/responsiveness/volume Maintenance of this gradient challenged by: i. slow leakage of K+ and Na+ along conc. gradients ii. stimulation of muscle & nerve cells Na+/K+ ATPase functions continuously to maintain Na+ & K+ gradients Active Transport Primary active transport • the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. Resting Membrane Potential Resting membrane potential (RMP) – Electrical potential energy produced by separation of oppositely charged particles across plasma membrane in all cells • Difference in electrical charge between two points is referred to as voltage • Cells that have a charge are said to be polarized – Voltage occurs only at membrane surface rest of cell is neutral + 𝑲 is Key Player in RMP • RMP maintained by the + + 𝑁𝑎 −𝐾 pump • Neuron & muscle cells “upset” this steady state RMP by intentionally + + opening gated 𝑁𝑎 and 𝐾 channels http://site.motifolio.com/images/Passive-and-active-fluxes-maintainthe-resting-membrane-potential-5111223.png Active Transport 2. Secondary Active Transport Also called cotransport Required energy is obtained indirectly from ionic gradients created by primary active transport Many active transport systems are coupled systems Antiporters transport one substance into cell while transporting a different substance out of cell e.g. Na+ -K+ ATPase Symporters transport two different substances in the same direction e.g. Na+ & amino acids or glucose, Na+, K+, Clcotransporter https://www.apsubiology.org/anatomy/2010/2010_Exa m_Reviews/Exam_1_Review/uni-sym-antiport.jpg Active Transport Secondary Active Transport + • Low 𝑁𝑎 concentration that is + maintained inside cell by 𝑁𝑎 + − 𝐾 pump strengthens sodium’s drive to want to enter cell + • 𝑁𝑎 can drag other molecules with it as it flows into cell through carrier proteins (usually symporters) in membrane Some sugars, amino acids, and ions are usually transported into cells via secondary active transport Vesicular Transport • Transport of large particles, macromolecules, and fluids across membrane in membranous sacs called vesicles • Requires energy supplied by ATP Vesicular transport processes include: – Endocytosis: transport into cell • 3 different types of endocytosis: phagocytosis, pinocytosis, receptor-mediated endocytosis – Exocytosis: transport out of cell – Transcytosis: transport into, across, and then out of cell – Vesicular trafficking: transport from one area or organelle in cell to another Vesicular Transport Endocytosis – Involves formation of protein-coated vesicles – Usually involve receptors; therefore can be a very selective process Substance being pulled in must be able to bind to its unique receptor – Some pathogens are capable of hijacking receptor for transport into cell – Once vesicle is pulled inside cell, it may: Fuse with lysosome or Undergo transcytosis Endocytosis mediated by protein coated pits Vesicular Transport Endocytosis Phagocytosis Pinocytosis • • The cell engulfs a large particle by forming a projecting pseudopod (“false foot”) around it and enclosing it within a membranous sac called a phagosome The cell “gulps” a drop of extracellular fluid containing solutes into tiny vesicles. No receptors are used, so the process is nonspecific. Receptor-mediated endocytosis • Extracellular substances bind to specific receptor proteins, enabling the cell to ingest and concentrate specific substances in protein-coated vesicles. Substances may be released inside the cell or digested in a lysosome. Vesicular Transport Exocytosis: process where material is ejected from cell Neurons Jump to Chapter 11 here o structural units of nervous system o Large, highly specialized cells that conduct impulses 3 functional regions: (plasma membrane very important in all regions!) 1. Receptive region 2. Conducting region 3. Secretory region Figure 11.5a Structure of a motor neuron. Neurons Special characteristics Extreme longevity (lasts a person’s lifetime) amitotic, with few exceptions High metabolic rate requires continuous supply of oxygen and glucose All have cell body and one or more processes Neuron Cell Body (Perikaryon or Soma) • large, spherical nucleus + granular cytoplasm biosynthetic centre: synthesizes proteins, membranes, chemicals extensive rough ER + ribosome clusters (Nissl bodies); also elaborate Golgi & lots of mitochondria. Why?? Most neuronal cell bodies are located in CNS • Nuclei: clusters of neuronal cell bodies in CNS • Ganglia: clusters of neuronal cell bodies in PNS Neurons Neuronal Processes: arm like processes that extend from cell body Dendrites: receptive (input) region; Convey incoming messages toward cell body • short, tapering, branched extensions; usually hundreds/cell body • enormous SA for reception from other neurons • conduct impulses toward cell body • short distance, graded potentials Neurons Axon: conducting region • arises from axon hillock; variable length (can be > 1m) • usu. 1 axon/neuron; branches at end into axonal terminals or axon telodendria (~10,000) • rate of conduction increases with axon diameter • Neurotransmitters convey information from one axon to the next • Axon has same organelles as cell body, but no Nissl bodies; axons quickly degenerate if cut Tracts: Bundles of neuronal axons in CNS Nerves: Bundles of neuronal axons in PNS Elaborate cytoskeleton in axon to move material to & from: • Anterograde: (eg: mitos, cytoskeleton, membrane parts, NTs) • Retrograde: (eg: organelles to be degraded/recycled) Neurons Axon: conducting region Myelin sheath Composed of myelin, a whitish, protein-lipid substance – Function of myelin • Protect and electrically insulate axon • Increase speed of nerve impulse transmission Figure 11.6a PNS nerve fiber myelination. A Clinical Note Multiple Sclerosis • persistent inflammatory response in which myelin sheaths gradually destroyed (autoimmune? persistent virus?) Turns myelin into hardened lesions called scleroses Impulse conduction slows and eventually ceases • cycles of remission and relapse: flare-ups and then some healing and myelin regeneration; axons develop more Na+ channels in demyelinated areas Symptoms: • blindness (optic nerve), muscle weakness, clumsiness, urinary incontinence • ultimately myelin destruction is permanent and axons “drop out” or degenerate https://www.mayoclinic.org/-/media/kcms/gbs/patientconsumer/images/2015/03/25/08/29/mcdc7_multiple_s clerosis_myelin_damage_nervous_system-8col.jpg Basic Principles of Electricity • Opposite charges are attracted to each other • Energy is required to keep opposite charges separated across a membrane • When opposite charges are separated, the system has potential energy • Energy is liberated when the charges move toward one another http://site.motifolio.com/images/Passive-and-active-fluxes-maintainthe-resting-membrane-potential-5111223.png Basic Principles of Electricity Definitions Voltage: a measure of potential energy generated by separation (PM) of oppositely charged ions • Measured between two points in volts (V) or millivolts (mV) • Called potential difference or potential • Charge difference across plasma membrane results in potential Greater charge difference between points = higher voltage Current: flow of electrical charge (ions) between two points • Flow is dependent on voltage & resistance; can be used to do work Resistance: hindrance to charge flow • Insulator: substance with high electrical resistance • Conductor: substance with low electrical resistance Basic Principles of Electricity Role of membrane ion channels • Large proteins serve as selective membrane ion channels • K+ ion channel allows only K+ to pass through Two main types of ion channels • Leakage (nongated) channels: always open • Gated channels, in which part of the protein changes shape to open/close the channel. 3 main gated channels: 1. Chemically gated Channels : open only with binding of a specific chemical (neurotransmitter/hormone) 2. Voltage−gated: open and close in response to changes in membrane potential 3. Mechanically gated: Open and close in response to physical deformation of receptors, as in sensory receptors Operation of Gated Channels channels ion-specific: channels open >> ions move in response to electrochemical gradients Generating the Resting Membrane Potentials • all cells are polarized; RMP cell-type-dependent • neurons have a resting membrane potential Membrane potential generated by: • Differences in ionic composition of Intracellular fluid and Extracellular Fluid – ECF has > concentration of + 𝑁𝑎 than ICF • Balanced chiefly by chloride ions (𝐶𝑙) – ICF has higher concentration of K+ than ECF • Balanced by negatively charged proteins – K+ plays the most important role in membrane potential Generating the Resting Membrane Potentials Differences in plasma membrane permeability • Impermeable to large anionic proteins • Slightly permeable to Na+ (through leakage channels) • Sodium diffuses into cell down concentration gradient • 25 times more permeable to K+ than sodium (more leakage channels) • Potassium diffuses out of cell down concentration gradient • Quite permeable to Cl– • Sodium-potassium pump (Na+/K+ ATPase) stabilizes resting membrane potential • Maintains concentration gradients for Na+ and K+ • Three Na+ are pumped out of cell while two K+ are pumped back in Generating the Resting Membrane Potentials Neurons are highly excitable What do we mean when we say that neurons are excitable cells?? A&P Flix™: Resting Membrane Potential Check your understanding Check all descriptions that apply to a resting neuron: 1. Its inside is negative relative to its outside. 2. Its outside is negative relative to its inside. 3. The cytoplasm contains more Na+ and less K+ than does the ECF. 4. The cytoplasm contains more K+ and less Na+ than does the ECF. 5. A charge separation exists at the plasma membrane. 6. The electrochemical gradient for the movement of Na+ across the membrane is greater than that for K+. 7. The electrochemical gradient for the movement of K+ across the membrane is greater than that for Na+. 8. The membrane is more permeable (leaky) to Na+ than to K+. 9. The membrane is more permeable (leaky) to K+ than to Na+. Changing the Resting Membrane Potential When does membrane potential change? Depolarization: decrease in membrane potential (moves toward zero & above) Inside of membrane becomes less negative than RMP Increases probability of producing impulse Hyperpolarization: increase in membrane potential (away from 0) Inside of membrane becomes more negative than RMP Decreases probability of producing impulse Changes produce two types of signals • Graded potentials: ……………… • Action potentials: ……………….. • Changes used as signals to receive, integrate and send information Graded Potentials Short-lived, localized changes in membrane potential • Triggered by stimulus that opens gated ion channels • Results in depolarization or sometimes hyperpolarization • The stronger the stimulus, the more voltage changes and the farther the current flows • decremental movement of ions on either side of membrane propagates signal for short distance Named according to location and function • Receptor potential (generator potential): graded potentials in receptors of sensory neurons • Postsynaptic potential: neuron graded potential Action Potentials Brief reversal of membrane potential with a change in voltage of ~100 mV (from -70 to +30 mV) in a patch of membrane depolarized by local currents • principal way neurons send signals • means of long-distance neural communication • do not decay in amplitude with distance traveled as graded potentials do • occur only in cells with excitable membranes (neurons & muscle cells) • in neurons • only axons can generate action potentials • also referred to as a nerve impulse voltage-gated channels on axons open & close in response to local currents (graded potentials) https://www.moleculardevices.com/sites/default/f iles/images/page/what-is-action-potential.jpg Generation of an Action Potential Four main steps 1. Resting state: All gated 𝑵𝒂+ and K+ channels are closed normal leakage Each Na+ channel has two voltagesensitive gates • Activation gates • Inactivation gates Each K+ channel has one voltagesensitive gate • Closed at rest • Opens slowly with depolarization local depolarization: voltage-gated Na+ channels open (fast activation gates) Generation of an Action Potential 2. Depolarization: Na+ channels open Depolarizing local currents open voltagegated Na+ channels, and Na+ rushes into cell – Na+ activation & inactivation gates open Na+ influx causes more depolarization, which opens more Na+ channels As a result, ICF becomes less –ve At threshold (–55 to –50 mV), positive feedback causes opening of all Na+ channels Results in large action potential spike Membrane polarity jumps to +30 mV Both Na+ gates must be open for entry; closure of either gate stops Na+ entry What does threshold (-55 to -50 mV) mean? Generation of an Action Potential 3. Repolarization: Na+ channels are inactivating, & K+ channels open Na+ channel inactivation gates close • AP spike stops rising Voltage-gated K+ channels open • K+ exits cell down its electrochemical gradient Repolarization: membrane returns to resting membrane potential Generation of an Action Potential 4. Hyperpolarization: some K+ channels remain open, & Na+ channels reset Some K+ channels remain open, allowing excessive K+ efflux Inside of membrane becomes more negative than in resting state This causes hyperpolarization of the membrane (slight dip below resting voltage) Na+ channels also begin to reset Propagation of an Action Potential AP must traverse length of the axon to signal next neuron Propagation rather than conduction of an AP • Na+ influx through voltage gates in one membrane area cause local currents that cause opening of Na+ voltage gates in adjacent membrane areas depolarization of that area, which in turn causes depolarization in next area APs are self propagating and unidirectional Since Na+ channels closer to the AP origin are still inactivated, no new AP is generated there AP occurs only in a forward direction Refractory Periods time in which neuron cannot trigger another AP • Voltage-gated Na+ channels are open, so neuron cannot respond to another stimulus Two types Absolute refractory period • Time from opening of Na+ channels until resetting of the channels • Ensures that each AP is an all-or-none event / enforces one-way transmission of nerve impulses Relative refractory period Follows absolute refractory period • • • • Figure 11.13 Absolute and relative refractory periods in an AP. Most Na+ channels have returned to their resting state Some K+ channels still open Repolarization is occurring Threshold for AP generation is elevated • Only exceptionally strong stimulus could stimulate an AP Coding for Stimulus Intensity • All action potentials are alike and are independent of stimulus intensity • CNS tells difference between a weak stimulus and a strong one by frequency of impulses • Frequency is number of impulses (APs) received per second • Higher frequencies mean stronger stimulus Threshold and All-or-None Phenomenon Conduction Velocity What two factors determine conduction velocity? Two types of conduction depending on presence or absence of myelin – Continuous conduction Conduction Velocity – • • • Saltatory conduction occurs only in myelinated axons & is about 30X faster Na+ channels located at gaps APs generated only at gaps THE SYNAPSE Neurons are functionally connected by synapses: junctions that mediate information transfer From one neuron to another neuron • Presynaptic vs postsynaptic neuron • most neurons are both Or from one neuron to an effector cell THE SYNAPSE 2 types of synapses: chemical and electrical CHEMICAL SYNAPSES • • Most common type specialized for the release and binding of neurotransmitters “Neurotransmitters . . .function to open or close ion channels that influence membrane permeability and, consequently, membrane potential.” (Marieb) Typically composed of two parts: – Axon terminal of presynaptic neuron: contains synaptic vesicles filled with neurotransmitter – Receptor region on postsynaptic neuron’s membrane: receives neurotransmitter Usually on dendrite or cell body Separated by synaptic cleft (fluid-filled space of 30-50 nm) INFORMATION TRANSFER ACROSS CHEMICAL SYNAPSES Six steps are involved: 1. AP arrives at axon terminal of presynaptic neuron 2. Voltage-gated Ca2+ channels open, Ca2+ enters axon terminal • Ca2+ flows down electrochemical gradient from ECF to inside of axon terminal 3. Ca2+ entry cause neurotransmitter release 4. Neurotransmitter diffuses across synaptic cleft and binds to postsynaptic receptors 5. Binding of neurotransmitter opens ion channels, creating graded potentials INFORMATION TRANSFER ACROSS CHEMICAL SYNAPSES 6. Neurotransmitter effects are terminated • As long as neurotransmitter is binding to receptor, graded potentials will continue, so process needs to be regulated • Within a few milliseconds, neurotransmitter effect is terminated in one of three ways • Reuptake by astrocytes or axon terminal • Degradation by enzymes • Diffusion away from synaptic cleft Synaptic Delay • Time needed for neurotransmitter to be released, diffuse across synapse, and bind to receptors • Can take anywhere from 0.3 to 5.0 ms • Synaptic delay is rate-limiting step of neural transmission • Transmission of AP down axon can be very quick, but synapse slows transmission to postsynaptic neuron down significantly • Not noticeable, because these are still very fast THE SYNAPSE ELECTRICAL SYNAPSES • Less common than chemical synapses • Neurons are electrically coupled • Joined by gap junctions that connect cytoplasm of adjacent neurons • Communication is very rapid and may be unidirectional or bidirectional • Found in some brain regions responsible for eye movements or hippocampus in areas involved in emotions and memory • Most abundant in embryonic nervous tissue Postsynaptic Potentials • Neurotransmitter receptors cause graded potentials that vary in strength based on: • Amount of neurotransmitter released • Time neurotransmitter stays in cleft • Depending on effect of chemical synapse, there are two types of postsynaptic potentials • EPSP: excitatory postsynaptic potentials • IPSP: inhibitory postsynaptic potentials Excitatory Synapses and EPSPs • Neurotransmitter binding opens chemically gated channels • Allows simultaneous flow of Na+ and K+ in opposite directions • Na+ influx greater than K+ efflux, resulting in local net graded potential depolarization called excitatory postsynaptic potential (EPSP) • EPSPs trigger AP if EPSP is of threshold strength • Can spread to axon hillock and trigger opening of voltage-gated channels, causing AP to be generated what is generated is NOT an AP; only axonal membranes can generate APs!!; get local, graded depolarizations called EPSPs; if strong enough to reach axon hillock, then get AP Inhibitory Synapses and IPSPs • Neurotransmitter binding to receptor opens chemically gated channels that allow entrance/exit of ions that cause hyperpolarization • Makes postsynaptic membrane more permeable to K+ or Cl– • If K+ channels open, it moves out of cell • If Cl– channels open, it moves into cell • Reduces postsynaptic neuron’s ability to produce an action potential • Moves neuron farther away from threshold (makes it more negative) Integration and Modification of Synaptic Events Summation by the postsynaptic neuron • A single EPSP cannot induce an AP, but EPSPs can summate (add together) to influence postsynaptic neuron • IPSPs can also summate • Most neurons receive both excitatory and inhibitory inputs from thousands of other neurons • Only if EPSPs predominate and bring to threshold will an AP be generated Two types of summations 1. Temporal 2. Spatial Postsynaptic Potentials and Their Summation Temporal summation • One or more presynaptic neurons transmit impulses in rapid-fire order • First impulse produces EPSP, and before it can dissipate another EPSP is triggered, adding on top of first impulse Postsynaptic Potentials and Their Summation Spatial summation • Postsynaptic neuron is stimulated by large number of terminals simultaneously • Many receptors are activated, each producing EPSPs, which can then add together