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Chapter 13 Signal Transduction Mechanisms: I. Electrical and Synaptic Signaling in Neurons Lectures by Kathleen Fitzpatrick Simon Fraser University © 2012 Pearson Education, Inc. Signal Transduction Mechanisms: I. Electrical and Synaptic Signaling in Neurons • Cell membranes can regulate the flow of ions between the interior and exterior of the cell • The most dramatic example of regulation of the electrical properties of cells is the nerve cell or neuron • Nerve cells have special mechanisms for using electrical potentials to transmit information over long distances © 2012 Pearson Education, Inc. Neurons • Almost all animals have a nervous system in which impulses are transmitted along the specialized plasma membranes of nerve cells • Vertebrates have a central nervous system (CNS), consisting of the brain and spinal cord, and a peripheral nervous system (PNS), which comprises other sensory or motor components © 2012 Pearson Education, Inc. Cells of the nervous system • The nervous system has two main types of cells – Neurons send and receive electrical impulses (nerve impulses) – Glial cells encompass a variety of cell types © 2012 Pearson Education, Inc. Neurons • Sensory neurons are a diverse group of cells specialized for the detection of stimuli • Motor neurons transmit signals from the CNS to the muscles and glands with which they make connections (innervate) • Interneurons process signals and transmit information between parts of the nervous system © 2012 Pearson Education, Inc. Glial cells • Microglia fight infections and remove debris • Oligodendrites and Schwann cells form the insulating myelin sheath around neurons of the CNS and peripheral nerves • Astrocytes control access of blood-borne components into the extra-cellular fluid around the nerve cells forming the blood-brain barrier © 2012 Pearson Education, Inc. Neurons Are Specially Adapted for the Transmission of Electrical Signals • The cell body of a neuron is similar to that of other cells, and includes the nucleus and other endomembrane components • Neurons also contain branches called processes • Processes that receive signals are dendrites and those that conduct signals are axons © 2012 Pearson Education, Inc. Axons • The cytosol within an axon is called axoplasm • Many vertebrate axons are surrounded by a discontinuous myelin sheath • The sheath insulates the segments of axon separating the nodes of Ranvier • A nerve is a tissue composed of bundles of axons © 2012 Pearson Education, Inc. Motor neurons • A motor neuron has multiple branched dendrites and a single axon, which is much longer than the dendrites • The branches terminate in structures called synaptic boutons (terminal bulbs, or synaptic knobs) • The boutons transmit the signal to the next cell, a neuron, muscle, or gland cell © 2012 Pearson Education, Inc. Synapses • The junction between a nerve cell, gland, or muscle cell is called a synapse • For neuron-to-neuron junctions, synapses occur between an axon and a dendrite, but they can also occur between two dendrites • Typically, neurons make synapses with other neurons, at the ends of axons and along their length as well © 2012 Pearson Education, Inc. Figure 13-1 © 2012 Pearson Education, Inc. Figure 13-1A © 2012 Pearson Education, Inc. Figure 13-1B © 2012 Pearson Education, Inc. Video: Neuron structure Right click on animation / Click play © 2012 Pearson Education, Inc. Understanding Membrane Potential • Membrane potential is a fundamental property of all cells • Cells at rest normally have excess negative charge on the outside and positive charge on the inside of the cell • The resulting electrical potential is called the resting membrane potential © 2012 Pearson Education, Inc. The squid giant axon • The very large squid giant axon has been used for studies of nerve transmission since the 1930s • It’s large size allows for easy insertion of microelectrodes to measure and control electrical potentials • The resting membrane potential can be measured © 2012 Pearson Education, Inc. Figure 13-2 © 2012 Pearson Education, Inc. Figure 13-3A © 2012 Pearson Education, Inc. Resting membrane potential • Electrodes compare the ratio of negative to positive charge inside and outside the cell • The resting membrane potential is about – 60mV for the squid giant axon • Nerve, muscle, and certain other cell types exhibit electrical excitability © 2012 Pearson Education, Inc. Electrically excitable cells • In electrically excitable cells, certain stimuli trigger a rapid set of changes in membrane potential • This is known as an action potential • During the action potential the membrane potential changes from negative to positive and then back again in a very short time © 2012 Pearson Education, Inc. Measuring changes in membrane potential • Microelectrodes can be used to measure changes in the membrane potential • The stimulating electrode is connected to a power source and inserted into the axon some distance from the recording electrode • A brief impulse from the stimulating electrode depolarizes the membrane, measured at the recording electrode © 2012 Pearson Education, Inc. Figure 13-3B © 2012 Pearson Education, Inc. The Resting Membrane Potential Depends on Differing Concentrations of Ions Inside and Outside the Neuron and on the Selective Permeability of the Membrane • The cytosol and extracellular fluid of a cell contain different compositions of anions and cations • Extracellular fluid contains dissolved salts, mostly sodium chloride • The cytosol contains potassium as its main cation due to the action of the Na+/K+ pump © 2012 Pearson Education, Inc. Potassium ions and the membrane potential • The uneven distribution of potassium ions inside and outside the cell is the potassium ion gradient • Because of this gradient, potassium ions will tend to diffuse out of the cell toward the region of lower concentration • Ions in solution are present in pairs, one negative and one positive (electroneutrality) © 2012 Pearson Education, Inc. Counterions • For any given ion, there must be an oppositely charged ion in the solution • The oppositely charged ion is called the counterion • In the cytosol, potassium (K+) ions serve as counterions for the trapped anions; outside the cell, Na+ is the main cation with Cl– as its counterion © 2012 Pearson Education, Inc. Electrical potential • A solution must have an equal number of positive and negative charges overall, but they can be unevenly distributed, with one region more positive and another more negative • Even when separated, they will tend to flow back toward each other (electric potential, or voltage) • When the oppositely charged ions are moving toward each other, current is flowing, measured in amperes (A) © 2012 Pearson Education, Inc. Resting potential forms as a result of ionic compositions inside and outside the cell • Some types of potassium channels in the plasma membrane allow K+ to diffuse out of the cell • As K+ leaves the cytosol, increasing numbers of anions are left behind without counterions • Excess negative charge accumulates outside the cell and excess positive charge accumulates outside, resulting in the membrane potential © 2012 Pearson Education, Inc. Figure 13-4 © 2012 Pearson Education, Inc. Figure 13-4A © 2012 Pearson Education, Inc. Figure 13-4B © 2012 Pearson Education, Inc. Equilibrium • K+ diffuses out of cell down its gradient, but eventually the gradient is balanced by the K+ electrical potential and net movement of K+ stops • When a chemical gradient is balanced by an electrical potential, it is called electrochemical equilibrium • The membrane potential at the point of equilibrium is known as an equilibrium (or reversal) potential © 2012 Pearson Education, Inc. The Nernst Equation Describes the Relationship Between Membrane Potential and Ion Concentration • The Nernst equation describes the mathematical relationship between an ion gradient and the equilibrium potential that will form when the membrane is permeable only to that ion • . © 2012 Pearson Education, Inc. The Nernst equation • The Nernst equation can be expressed as © 2012 Pearson Education, Inc. The Na+/K+ pump • The Na+/K+ pump continually pumps sodium ions out of the cell to compensate for the small amount of leakage of sodium into the cell • At the same time, potassium is carried inward • On average, three sodium are transported inward for every two potassium ions transported outward © 2012 Pearson Education, Inc. Steady-State Concentrations of Common Ions Affect Resting Membrane Potential • Equation 13-2 is not complete because it doesn’t account for the effects of anions • Because of the unequal distributions of Na+, K+, and Cl– across the membrane, each has a different impact on the membrane potential • Each ion diffuses down its electrochemical gradient and affects the membrane potential © 2012 Pearson Education, Inc. Figure 13-5 © 2012 Pearson Education, Inc. Figure 13-5A © 2012 Pearson Education, Inc. Figure 13-5B © 2012 Pearson Education, Inc. Figure 13-5C © 2012 Pearson Education, Inc. Effect of ions on membrane potential • K+ tends to diffuse out of the cell, making the membrane potential more negative • Na+ tends to flow into the cell, driving the potential in the positive direction, causing depolarization • Cl– tends to diffuse into the cell but is repelled by the negative membrane potential, so enters along with positive ions © 2012 Pearson Education, Inc. Increased membrane permeability to Cl– decreases excitability • Increasing the membrane permeability to chloride has two effects, and both decrease neuronal excitability – The net entry of chloride ions (without a matching cation) causes hyperpolarization (membrane potential is more negative) – When the membrane becomes permeable to sodium, some chloride will also enter © 2012 Pearson Education, Inc. The Goldman Equation Describes the Combined Effects of Ions on Membrane Potential • Even in the resting state the cell is a little permeable to sodium, chloride, and potassium ions • The Nernst equation doesn’t account for leakage of sodium and chloride into the cell; it deals with just one ion at a time • It is helpful to consider the steady-state ion movements across the membrane © 2012 Pearson Education, Inc. Steady-state movement of ions across the plasma membrane • A membrane permeable only to K+ will have a membrane potential equal to the equilibrium potential for K+ • If the membrane is also slightly permeable to Na+, the membrane potential will be partially depolarized as Na+ leaks into the cell • There is now less restraint on K+ leaving the cell, so K+ diffuses outward, balancing the inward movement of Na+ © 2012 Pearson Education, Inc. Figure 13-6 © 2012 Pearson Education, Inc. Figure 13-6A © 2012 Pearson Education, Inc. Figure 13-6B © 2012 Pearson Education, Inc. Goldman, Lloyd, and Katz • These were the first researchers to describe how gradients of several different ions each contribute to a membrane potential • Their equation, known as the Goldman equation, is © 2012 Pearson Education, Inc. Goldman equation • The Goldman equation, unlike the Nernst equation, includes terms for permeability of the ions involved • In this case PK, Pna, and PCl are the relative permeabilities for each ion • Except under special circumstances, the contribution of other ions to membrane potential is negligible © 2012 Pearson Education, Inc. An example of the Goldman equation • To estimate resting membrane potential in a squid axon, we use known steady-state concentrations and relative permeabilities of the three ions • K+ can be assigned a permeability value of 1.0 and the others are determined relative to that • The relative permeability of Na+ is 4% (0.04) and Cl– is 45% (0.45) © 2012 Pearson Education, Inc. An example of the Goldman equation • Using the relative permeabilities and the concentrations of the ions from Table 13-1, one can estimate resting potential of the squid axon • This comes to –60.3 mV © 2012 Pearson Education, Inc. Table 13-1 © 2012 Pearson Education, Inc. Nernst and Goldman equations • When the relative permeability of one of the ions is very high, the Goldman equation reduced to the Nernst equation for that ion • For instance, if we ignore the effect of Cl–, as we can when Pna → PK © 2012 Pearson Education, Inc. Electrical Excitability • The unique feature of electrically excitable cells is their response to depolarization • Excitable cells respond with an action potential • Excitable cells have voltage-gated channels in their plasma membranes © 2012 Pearson Education, Inc. Ion Channels Act Like Gates for the Movement of Ions Through the Membrane • Ion channels: integral membrane proteins that form ion-conducting pores in the lipid bilayer • Voltage-gated ion channels respond to changes in the voltage across a membrane • Voltage-gated Na+ and K+ channels are responsible for the action potential © 2012 Pearson Education, Inc. Other ion channels • Ligand-gated ion channels open when a ligand binds to the channel • Other channels contribute to the steady-state ionic permeability of membranes • These leak channels allow cells to be somewhat permeable to cations © 2012 Pearson Education, Inc. Patch Clamping and Molecular Biological Techniques Allow the Activity of Single Ion Channels to Be Monitored • Patch clamping, or single-channel recording, records currents passing through individual channels © 2012 Pearson Education, Inc. Figure 13-7 © 2012 Pearson Education, Inc. Patch Clamping • An amplifier keeps the membrane at a fixed membrane potential despite changes in its electrical properties • Then the voltage clamp measures tiny changes in current flow through individual channels © 2012 Pearson Education, Inc. Conductance • Conductance is an indirect measure of the permeability of a channel when a particular voltage is applied • It is the inverse of resistance © 2012 Pearson Education, Inc. Specific Domains of Voltage-Gated Channels Act as Sensors and Inactivators • Voltage-gated potassium channels are multimeric proteins, composed of four protein subunits • Voltage-gated sodium channels are large monomeric proteins with four separate domains • In both types of channels each domain or subunit contains six transmembrane -helices © 2012 Pearson Education, Inc. Figure 13-8A © 2012 Pearson Education, Inc. Channel specificity • The size of the central pore and the way it interacts with an ion gives the channel its specificity • Oxygen atoms in the amino acids at the center of the channel are positioned to interact with ions as they move through the selectivity filter © 2012 Pearson Education, Inc. Channel gating • Voltage-gated sodium channels can open rapidly in response to a stimulus and then close again; channel-gating • The open or closed state is all-or-none; the channels are not partially open • The fourth subunit, S4, acts as a voltage sensor, responding to changes in potential © 2012 Pearson Education, Inc. Figure 13-8C © 2012 Pearson Education, Inc. Channel inactivation • Most voltage-gated channels adopt a second type of closed state, channel inactivation • When a channel is inactivated it cannot reopen immediately, even if stimulated to do so • Inactivation is caused by part of the channel called the inactivation particle that inserted in the opening of the channel © 2012 Pearson Education, Inc. Figure 13-9 © 2012 Pearson Education, Inc. The Action Potential • The coordinated opening and closing of ion channels leads to an action potential • The giant axon of the squid has been important in the study of action potential © 2012 Pearson Education, Inc. Action Potentials Propagate Electrical Signals Along an Axon • Depolarization that brings the membrane to the threshold potential initiates an action potential • An action potential is a brief but large electrical depolarization and repolarization of the neuronal plasma membrane • It is caused by inward movement of sodium and subsequent outward movement of potassium © 2012 Pearson Education, Inc. Action Potentials • Movement of sodium and potassium ions during the action potential are controlled by the opening and closing of voltage-gated channels • Once the action potential is initiated it will travel along the membrane away from the origin by a process called propagation © 2012 Pearson Education, Inc. Action Potentials Involve Rapid Changes in the Membrane Potential of the Axon • Development and propagation of an action potential (all within a few milliseconds) – Membrane potential rises dramatically to about +40 mV – It then falls slowly to about –75 mV (undershoot, or hyperpolarization) – It stabilizes again at the resting potential of about –60 mV © 2012 Pearson Education, Inc. Action Potentials Result from the Rapid Movement of Ions Through Axonal Membrane Channels • In a resting neuron the voltage-dependent channels are usually closed • Because of leakiness to K+, the cell is about 100 times more permeable to K+ than to Na+ • When a region of the nerve cell is slightly depolarized, some of the Na+ channels open © 2012 Pearson Education, Inc. Rapid movement of ions through axonal membrane channels • The increased flow of Na+ through the channels increases membrane depolarization • Increasing depolarization opens more channels, causing more Na+ to flow, etc. • This positive feedback loop is called the Hodgkin cycle © 2012 Pearson Education, Inc. Subthreshold Depolarization • When the membrane is depolarized by a small amount, the membrane potential recovers because of K+ movement through leak channels • In this case no action potential occurs • Levels of depolarization too small to initiate an action potential are called subthreshold depolarizations © 2012 Pearson Education, Inc. The Depolarizing Phase • When the membrane is depolarized past the threshold potential a significant number of Na+ channels begin activating • The membrane potential shoots upward rapidly • It peaks at about +40 mV © 2012 Pearson Education, Inc. Figure 13-10 © 2012 Pearson Education, Inc. Figure 13-10A © 2012 Pearson Education, Inc. Figure 13-10B © 2012 Pearson Education, Inc. The Repolarizing Phase • Once the membrane potential has risen to its peak the membrane quickly repolarizes • This is due to inactivation of sodium channels and opening of voltage-gated potassium channels • The inactivated sodium channels remain closed until the membrane potential is negative again • The cell repolarizes as K+ leaves the cell © 2012 Pearson Education, Inc. The Hyperpolarizing Phase (Undershoot) • At the end of an action potential most neurons show a transient hyperpolarization or undershoot • The membrane potential temporarily drops below the resting potential. This occurs because of increased potassium permeability. • As the voltage-gated potassium channels close, the membrane potential returns to normal © 2012 Pearson Education, Inc. The Refractory Periods • For a few milliseconds after an action potential, it is impossible to trigger a second one • This is the absolute refractory period, when sodium channels are inactivated and cannot open by depolarization • During undershoot, sodium channels can open again but potassium channels are open, too © 2012 Pearson Education, Inc. Refractory Periods • Potassium leak channels and voltage-gated channels are open, driving the membrane potential down • This is well below the threshold for triggering another action potential • This time is called the relative refractory period © 2012 Pearson Education, Inc. Changes in Ion Concentrations Due to an Action Potential • During an action potential, cellular concentrations of Na+ and K+ hardly change at all • The ions involved are a small fraction of the total ions in the cell • Intense neuronal activity can lead to significant changes in ion concentration © 2012 Pearson Education, Inc. Action Potentials Are Propagated Along the Axon Without Losing Strength • Depolarization that occurs in one place along a membrane spreads to adjacent regions through passive spread of depolarization • As it spreads away from the origin it decreases in magnitude, so signals cannot travel far by this means • To go farther, the action potential must be propagated, actively generated without fading as it moves © 2012 Pearson Education, Inc. Figure 13-11 © 2012 Pearson Education, Inc. Transmission of a signal • Incoming signals are transmitted to a neuron at points of contact called synapses • Incoming signals depolarize the dendrites and the depolarization spreads passively over the membrane to the base of the axon, the axon hillock • This is where action potentials are most easily generated © 2012 Pearson Education, Inc. Propagation of an action potential in a nonmyelinated nerve cell • Stimulation of a resting membrane results in depolarization and an inward rush of Na+ (1) • Membrane polarity is temporarily reversed and this spreads (2) • Nearby depolarization is above a threshold, and results in an inward movement of Na+ (3) © 2012 Pearson Education, Inc. Figure 13-12, Steps 1-3 © 2012 Pearson Education, Inc. Propagation of an action potential (continued) • The original region on the membrane becomes permeable to K+ ions, which rush out of the cell, and return the membrane to its resting state (4) • Meanwhile, depolarization has spread farther, initiating the same sequence of events there (5) • The propagation of these events is a propagated action potential or nerve impulse © 2012 Pearson Education, Inc. Figure 13-12, Steps 4-5 © 2012 Pearson Education, Inc. The Myelin Sheath Acts Like an Electrical Insulator Surrounding the Axon • Most vertebrate axons are surrounded by many concentric layers of membrane, forming a discontinuous myelin sheath • It is formed by oligodendrites in the CNS and Schwann cells in the PNS © 2012 Pearson Education, Inc. Figure 13-13 © 2012 Pearson Education, Inc. Figure 13-13A © 2012 Pearson Education, Inc. Figure 13-13C © 2012 Pearson Education, Inc. Consequences of myelination • Myelination decreases the ability of the neuronal membrane to retain electric charge (i.e., capacitance) • Nerve impulses can spread farther and faster than in the absence of myelination • The action potential must still be renewed; this happens at nodes of Ranvier © 2012 Pearson Education, Inc. Action potentials are renewed at nodes of Ranvier • Nodes of Ranvier are spaced closely enough to ensure the action potential at one node can trigger one in the next node • Action potentials jump from one node to the next, called saltatory propagation, more rapid than continuous propagation • Nodes of Ranvier are highly organized structures © 2012 Pearson Education, Inc. Figure 13-13B © 2012 Pearson Education, Inc. Figure 13-14, Steps 1-3 © 2012 Pearson Education, Inc. Figure 13-14, Steps 4-5 © 2012 Pearson Education, Inc. Synaptic Transmission • Nerve cells communicate with one another and other cell types at synapses • Electrical synapse: one neuron (presynaptic) is connected to a second neuron (postsynaptic) via gap junctions • Ions move through the junctions between the cells and there is no delay in transmission © 2012 Pearson Education, Inc. Figure 13-15 © 2012 Pearson Education, Inc. Figure 13-15A © 2012 Pearson Education, Inc. Figure 13-15B © 2012 Pearson Education, Inc. Chemical synapses • Chemical synapse: presynaptic and postsynaptic neurons are not connected by gap junctions • Instead the two cell membranes are separated by a small space, the synaptic cleft • A signal at the terminus of the presynaptic neuron must be sent to the postsynaptic neuron chemically © 2012 Pearson Education, Inc. Figure 13-16 © 2012 Pearson Education, Inc. Figure 13-16A © 2012 Pearson Education, Inc. Figure 13-16B © 2012 Pearson Education, Inc. Figure 13-16C © 2012 Pearson Education, Inc. Neurotransmitters • Neurotransmitters are stored in synaptic boutons in the presynaptic neuron, released by the arrival of an action potential • They diffuse across the cleft and bind to receptors in the plasma membrane of the postsynaptic cell • They are converted into electric signals, to stimulate or inhibit an action potential in the receiving cell © 2012 Pearson Education, Inc. Types of neurotransmitter receptors • Neurotransmitter receptors fall into two classes – Ligand-gated ion channels (ionotropic receptors) – Receptors that exert their effects indirectly via a system of messengers (metabotropic receptors) © 2012 Pearson Education, Inc. Figure 13-17 © 2012 Pearson Education, Inc. Figure 13-17A © 2012 Pearson Education, Inc. Figure 13-17B © 2012 Pearson Education, Inc. Neurotransmitters Relay Signals Across Nerve Synapses • Neurotransmitter: any signaling molecule released by a neuron, detected by the postsynaptic cell through a receptor • Excitatory receptors: cause depolarization of the postsynaptic neuron • Inhibitory receptors: cause the postsynaptic cell to hyperpolarize © 2012 Pearson Education, Inc. Criteria for neurotransmitters • To qualify as a neurotransmitter a molecule must - 1. Elicit the appropriate response when introduced to the synaptic cleft - 2. Occur naturally in the presynaptic neuron - 3. Be released at the right time when the presynaptic neuron is stimulated © 2012 Pearson Education, Inc. Table 13-2 © 2012 Pearson Education, Inc. Acetylcholine • Acetylcholine is the most common neurotransmitter in vertebrates in synapses outside the CNS and for neuromuscular junctions • It is an excitatory neurotransmitter • Synapses using acetylcholine as their neurotransmitter are called cholinergic synapses © 2012 Pearson Education, Inc. Catecholamines • Catecholamines include dopamine and the hormones norepinephrine and epinephrine • All are derivatives of tyrosine, and are also synthesized in the adrenal gland • Synapses (in the brain and between nerves and smooth muscles in internal organs) that use catecholamines as neurotransmitters are called adrenergic © 2012 Pearson Education, Inc. Amino Acids and Derivatives • Some other neurotransmitters consist of amino acids and their derivatives: histamine, serotonin, g-amino butyric acid (GABA) as well as glycine and glutamate • Serotonin is excitatory (causes potassium channels to close) and functions in the CNS • GABA and glycine are inhibitory; glutamate is excitatory © 2012 Pearson Education, Inc. Neuropeptides • Neuropeptides are short amino acid chains formed by proteolysis of precursor proteins • Hundreds are known; they act on groups of neurons and have long-lasting effects • E.g., enkephalins inhibit the activity of neurons in the brain that are involved in pain perception © 2012 Pearson Education, Inc. Elevated Calcium Levels Stimulate Secretion of Neurotransmitters from Presynaptic Neurons • Neurotransmitter secretion is directly controlled by calcium ion concentration in synaptic boutons • When an action potential arrives, depolarization causes a temporary increase in Ca2+ due to opening of voltage-gated calcium channels • The neurotransmitters are stored in small neurosecretory vesicles in the bouton © 2012 Pearson Education, Inc. Figure 13-18 © 2012 Pearson Education, Inc. Neurotransmitter release • The release of calcium into the bouton has two effects - 1. Vesicles in storage are mobilized for rapid release - 2. Vesicles near the membrane that are poised for release fuse with the plasma membrane and expel the contents into the cleft © 2012 Pearson Education, Inc. Video: How synapses work Use window controls to play © 2012 Pearson Education, Inc. Secretion of Neurotransmitters Involves the Docking and Fusion of Vesicles with the Plasma Membrane • Vesicle fusion is thought to involve vesicles that are already “docked” at the plasma membrane • Docking and fusion are mediated by t- and v-SNARE proteins • Ca2+ in the boutons is bound by synaptogamin, which undergoes conformational change and promotes t- and v-SNARES to interact efficiently © 2012 Pearson Education, Inc. The active zone • Docking takes place at the active zone where the synaptic vesicles and calcium channels are very close together • Neurotoxins such as tetanus and botulism interfere with docking and release • Compensatory endocytosis maintains the size of the nerve terminal by recycling membranes © 2012 Pearson Education, Inc. Figure 13-19 © 2012 Pearson Education, Inc. Figure 13-19A © 2012 Pearson Education, Inc. Figure 13-19B © 2012 Pearson Education, Inc. Kiss-and-run exocytosis • When neurons need to fire very rapidly they use a more transient method for neurotransmitter release • A vesicle will temporarily fuse with the plasma membrane, release some neurotransmitter, and then reseal • This is called kiss-and-run exocytosis © 2012 Pearson Education, Inc. Neurotransmitters Are Detected by Specific Receptors on Postsynaptic Neurons • Each neurotransmitter has a particular receptor that detects and binds it • A few of these receptors are quite well understood © 2012 Pearson Education, Inc. The Nicotinic Acetylcholine Receptor • Acetylcholine binds a ligand-gated Na+ channel called the nicotinic acetylcholine receptor (nAchR) • When two molecules of acetylcholine bind, the receptor opens and lets Na+ rush into the cell, causing depolarization • nAchR has been studied using the electric organ of the electric ray (Torpedo californica) © 2012 Pearson Education, Inc. NAchR structure • The receptor forms rosette-like particles about 8 nm across • It consists of four kinds of subunits (, b, g, d) • The receptors play an important role in transmitting nerve impulses to muscle; in humans, autoimmune reactions against these receptors cause serious illnesses © 2012 Pearson Education, Inc. Figure 13-20 © 2012 Pearson Education, Inc. Figure 13-20A © 2012 Pearson Education, Inc. Figure 13-20B © 2012 Pearson Education, Inc. Figure 13-20C © 2012 Pearson Education, Inc. Video: The acetycholine receptor Use window controls to play © 2012 Pearson Education, Inc. The GABA Receptor • The GABA receptor is also a ligand-gated channel, but when opened, it allows Cl– ions into the cell • This causes hyperpolarization of the receiving cell and decreased likelihood that an action potential will be generated © 2012 Pearson Education, Inc. Neurotransmitters Must Be Inactivated Shortly After Their Release • Once the neurotransmitter has been secreted, it must be rapidly removed from the synaptic cleft • Acetylcholinesterase hydrolyzes acetylcholine • Neurotransmitter reuptake involves pumping neurotransmitters back into the presynaptic cell or nearby support cells © 2012 Pearson Education, Inc. Integration and Processing of Nerve Signals • A single action potential is usually not enough to cause firing of a postsynaptic cell • Incremental changes in potential due to neurotransmitter binding are called postsynaptic potentials (PSPs) • These can cause excitatory or inhibitory postsynaptic potentials depending on the neurotransmitter © 2012 Pearson Education, Inc. Neurons Can Integrate Signals from Other Neurons Through Both Temporal and Spatial Summation • Individual action potentials will produce only a temporary EPSP • Two action potentials in rapid succession will result in a more depolarized receiving cell • A rapid series of action potentials sums EPSPs over time, and pushes the postsynaptic cell past its threshold (temporal summation) © 2012 Pearson Education, Inc. Spatial summation • Action potentials received at a single synapse are usually not sufficient to induce an action potential • When many action potentials cause neurotransmitter release simultaneously, it is more likely that an action potential will be induced • This is called spatial summation © 2012 Pearson Education, Inc. Neurons Can Integrate Both Excitatory and Inhibitory Signals from Other Neurons • Postsynaptic neurons can receive both inhibitory and excitatory signals • Neurons can receive thousands of inputs from other neurons, and physically sum EPSPs and IPSPs © 2012 Pearson Education, Inc. Figure 13-21 © 2012 Pearson Education, Inc. Figure 13-21A © 2012 Pearson Education, Inc. Figure 13-21B © 2012 Pearson Education, Inc.