Neurons and the Nervous System 2 PDF

Neurons and the Nervous System 2 Resting potential = -70mV. The nervous signal is a transient depolarization; = the action potential The action potential is followed by repolarization and transient hyperpolarization. cytosol plasma membran...

Neurons and the Nervous System 2 Resting potential = -70mV. The nervous signal is a transient depolarization; = the action potential The action potential is followed by repolarization and transient hyperpolarization. cytosol plasma membrane organic anions- K+ (e.g. proteins) - + ~-70mV Cl- K+ Cl- Na+ Na+ Higher [K+] inside. Higher [Na+] outside.  Neurons and the Nervous System 2 The electrical signal is an action potential that moves down the axon. The action potential is a depolarization (decrease in voltage) followed by a repolarization. Then a hyperpolarization, and finally back to the resting potential. Changes in membrane potential (voltage) over time at one node of Ranvier. Threshold potential Modified from OpenStax Anatomy and Physiology Resting potential  Neurons and the Nervous System 2 At one node of Ranvier on the axon: When the membrane potential goes above 0 volts, the outside of the PM is negative relative to the cytosol. Graph of Action Potential: Plotting voltage measured across the cell membrane against time, the action potential begins with depolarization, followed by repolarization, which goes past the resting potential into hyperpolarization, and finally the membrane returns to rest. OpenStax Anatomy and Physiology  Neurons and the Nervous System 2 At one node of Ranvier on the axon: OpenStax Anatomy and Physiology Threshold potential. Resting potential. Stimulus (= a depolarization) received. The stimulus (depolarization) must exceed the threshold potential for an action potential to be generated.  Neurons and the Nervous System 2 Summation of incoming signals at the axon hillock (and adjacent downstream portion of neuron). The signals are action potentials generated by upstream neurons. The upstream neurons send signals to the dendrites or the cell body. If the summed signals at the axon hillock are large enough (larger than the threshold potential) → action potential. synaptic nucleus terminal dendrite cell body/soma = terminal bouton axon Schwann = axon terminal hillock cell node of Ranvier axon direction of signal  Neurons and the Nervous System 2 The nervous signal is an action potential that moves down the axon. The action potential is a depolarization (decrease in voltage) followed by a repolarization. Modified from: en:User:Chris 73, updated by en:User:Diberri, converted to SVG by tiZom Creative Commons Attribution-Share Alike 3.0 Repolarization Hyperpolarization If the stimulus (depolarization) does not exceed the threshold potential, there is no action potential.  Neurons and the Nervous System 2 The axon hillock adds up (integrates) the impulses coming in from upstream neurons; -if there are sufficient additive signals, the axon hillock will initiate an action potential that travels down the axon Release of neurotransmitters The action potential “jumps” down the into the synaptic ‘Action Potential Propagation’ by Casey Henley is licensed neuron, from one node of Ranvier to the under a Creative Commons Attribution Non-Commercial cleft. Share-Alike (CC-BY-NC-SA) 4.0 International License. next node of Ranvier.  Neurons and the Nervous System 2 If the summation at the axon hillock leads to a depolarization at the axon hillock that exceeds the threshold potential, then there is the initiation of an action potential. If the threshold potential is not exceeded, the depolarization fades away. Modified from: en:User:Chris 73, updated by en:User:Diberri, fast resting converted to SVG by tiZom Creative Commons Attribution-Share Alike goes I 3.0 Repolarization s Hyperpolarization If the stimulus (depolarization) does not exceed the threshold potential, there is no action potential. Not k Atpase brings back equilibrium  Neurons and the Nervous System 2 There are transport proteins that are involved in determining/changing the voltage across the PM of a neuron 1) Na+/K+-ATPase (Na+/K+ pump, Na+/K+-translocating ATPase); we have seen this before. All animal cells have this ATPase in the plasma membrane, including neurons. Activity of this ATPase leads to Δ[Na+] and Δ[K+] across the neuron plasma membrane; → a major contributor to the resting potential plasma membrane higher [Na+] lower [K+] 2K+ ADP + Pi lower [Na+] higher [K+] ATP 3Na+ Na+/K+ Pump - = Na+/K+-ATPase +  Neurons and the Nervous System 2 2) Voltage-gated ion channels There are voltage-gated Na+ and K+ channels in the neuron plasma membrane. Voltage-gated channels are closed at the resting potential, but open in response to changes in voltage (voltage acts as the “gate” that opens the channel). Voltage-gated ion channels show specificity; -Na+ channels allow the diffusion of Na+ down Δ[Na+] -K+ channels allow the diffusion of K+ down Δ[K+] The sequential opening and closing of these channels leads to depolarization and then repolarization (more details to come). The opening and closing of voltage-gated ion channels is controlled by the voltage (potential) across the membrane. By Efazzari - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curi d=47402716  Neurons and the Nervous System 2 To generate a depolarization: Open the voltage-gated Na+ channels; → depolarization Depolarization because positive charges are moving to the negative inside of the cell. cytosol plasma membrane organic anions- K+ (e.g. proteins) - + Cl- K+ Cl- Na+ Na+ ma In voltage-gated Na+ channel  Neurons and the Nervous System 2 Repolarization & Hyperpolarization: Close the voltage-gated Na+ channels and open the voltage-gated K+ channels; → repolarization and transient hyperpolarization cytosol plasma membrane organic anions- K+ (e.g. proteins) - + Cl- K+ Cl- chterge Na+ Na+ leaves voltage-gated K+ channel  Neurons and the Nervous System 2 Closing of the K+ channels. Followed by the re-establishment of the correct Δ[Na+] and Δ[K+], and the resting potential; → Na+/K+-ATPase (Na+/K+ pump) cytosol plasma membrane organic anions- K+ (e.g. proteins) - + 2K+ ADP + Pi Cl- K+ Cl- Na+ Na+ ATP Na+/K+-ATPase 3Na+  Neurons and the Nervous System 2 If the stimulus generated by the axon hillock is sufficiently large (exceeds the threshold potential): → voltage-gated Na+ channels open → Na+ (= positive charge) rapidly diffuses into the cell → depolarization Na+ channels are open, K+ not yet open depolar Sodium open potassium slated If the stimulus generated by the axon hillock is small; → failure to initiate an action potential Modified from: en:User:Chris 73, updated by en:User:Diberri, converted to SVG by tiZom Creative Commons Attribution-Share Alike 3.0  Neurons and the Nervous System 2 Next, the Na+ channels close, and the voltage-gated K+ channels open: → K+ (= positive charge) rapidly diffuses out of the cell → repolarization and then some overshoot (hyperpolarization) K+ channels are open, Na+ channels close Nat s closed replar back kt goal open here Modified from: Hyperpolarization en:User:Chris 73, updated by en:User:Diberri, converted to SVG by tiZom Creative Commons Attribution-Share Alike 3.0  Neurons and the Nervous System 2 Closing of the voltage-gated K+ channels. The Na+/K+-ATPase acts to restore the original Δ[Na+] and Δ[K+]; -pump out Na+ -pump in K+ → leads to repolarization after the hyperpolarization Refractory period The refractory period is a brief period (less than milliseconds) in which a node of Ranvier cannot “fire” (propagate an action potential); doesn't → will come back to this Repolarization Modified from: do anything en:User:Chris 73, updated by en:User:Diberri, converted to SVG by tiZom Creative Commons Attribution-Share Alike 3.0 af of thit happens one node of Ranvier  OpenStax Biology 2e A review, in pictures, of what we just covered. Resting potential, with Na+/K+-ATPase activity. Voltage-gated channels are closed. Na+ channel opens; depolarization. Na+ channel closes. K+ channel opens; hyperpolarization.  Neurons and the Nervous System 2 Saltatory conduction of the signal in myelinated neurons. Saltatory – derived from Latin “saltatorius” (to dance); = proceeding by abrupt movements or leaps; discontinuous (e.g. saltatory spiders are the “jumping spiders”) ummmm mmmmm Axon hillock Action potential “jumping” from node Modified from: Dhp1080 of Ranvier to the next node of Ranvier Creative Commons Attribution-Share Alike 3.0  Neurons and the Nervous System 2 OpenStax Biology 2e The action potential “leaps” or “jumps” from one node of Ranvier to the next. This is made possible by the myelin sheath (an insulator) and is an adaptation for rapid transmission of the signal. Myelinated axons transmit signals faster than non-myelinated axons; -myelinated axons typical of jawed vertebrate axons -some non-vertebrate groups also have similar types of sheaths on their axons Nation flowing in The depolarization at a particular node of Ranvier will travel in both directions, but useful travel is only in one direction (down the axon is useful, up the axon is not useful). How to prevent the upstream depolarization from leading to an action potential? → refractory period prevents that  Neurons and the Nervous System 2 Summary of Saltatory Conduction Action potential “jumps” or “leaps” down the axon, from one Node of Ranvier to the next downstream Node pf Ranvier. Depolarization followed by repolarization at successive Nodes of Ranvier. Axon hillock Action potential “jumping” from one node Modified from: Dhp1080 of Ranvier to the next node of Ranvier. Creative Commons Attribution-Share Alike 3.0  Neurons and the Nervous System 2 Refractory Period Refractory period The refractory period is a brief period (less than milliseconds) in which a Node of Ranvier cannot “fire” (propagate an action potential). Modified from: en:User:Chris 73, updated by en:User:Diberri, converted to SVG by tiZom Creative Commons Attribution-Share Alike 3.0  Neurons and the Nervous System 2 Refractory Period After an action potential has a passed a particular location (Node of Ranvier), that node cannot generate an action potential for a brief period; = the “refractory period” The refractory period is initiated by the temporary inactivation of the voltage-gated Na+ channels; → they remain closed, even if there is a depolarization Refractory period Modified from: en:User:Chris 73, updated by en:User:Diberri, converted to SVG by tiZom Creative Commons Attribution-Share Alike 3.0  Neurons and the Nervous System 2 Direction of signal Voltage-gated Na+ channel. Node of Ranvier. diffusion diffusion Schwann cell. Na+ ions The neuron “does not want” these Na+ ions to trigger an The neuron “wants” these Na+ ions action potential at the next to trigger an action potential at the node of Ranvier. next node of Ranvier. Refractory Period When a Na+ channel opens at a node of Ranvier, Na+ enters the axon. The Na+ will diffuse in both directions inside the axon. The refractory period prevents “upstream” Na+ diffusion from initiating an action potential. Maintains unidirectional movement of the nervous signal.  Neurons and the Nervous System 2 Action Potentials – Summary An action potential is a rapid depolarization/repolarization across the axon plasma membrane. Three types of transport proteins are involved: 1) voltage-gated Na+ channel 2) voltage-gated K+ channel 3) Na+/K+ pump (= Na+/K+-ATPase) The action potential is generated at the axon hillock (and just downstream of the axon hillock). The action potential “jumps” down the axon (salutatory conduction), until it reaches the axon terminal. A “refractory period” prevents upstream-moving depolarizations from triggering an action potential.  Neurons and the Nervous System 2 Transmitting the Nervous Signal between Neurons one neuron to another The most common type (but not the only type) of synapse is the chemical synapse. A chemical signal (neurotransmitter) is released by the presynaptic neuron (= the upstream neuron). The chemical signal generates an action potential in the post-synaptic neuron (= the downstream neuron). Laboratoires Servier Creative Commons Attribution-Share Alike 3.0 Synaptic Presynaptic neuron cleft/gap) Postsynaptic neuron A chemical synapse between two neurons. Vesicles with neurotransmitters direction of signal exocytosis  Neurons and the Nervous System 2 Terminology about Synapses: terms to know Synapse - The junction between two neurons, where the signal passes from one neuron to the next. Synaptic cleft (= synaptic gap) – The narrow space between the synaptic terminal of the pre-synaptic neuron and the post-synaptic neuron in a chemical synapse; the part of the post-synaptic cell forming the cleft could be a dendrite or the cell body. Electrical synapse - A synapse in which an electrical signal is directly transferred from one neuron to the next; not as common as a chemical synapse. Chemical synapse - A synapse in which the electrical signal of the pre-synaptic cell is transformed into a chemical signal in the synaptic cleft; the chemical signal triggers the formation of an electric signal in the post-synaptic cell; most common type of synapse; this is the one that we will examine. Information flow in a chemical synapse: action potential chemical signal action potential presynaptic cell synaptic cleft post-synaptic cell  Neurons and the Nervous System 2 action potential = electrical signal An example of a chemical synapse. neurotransmitters = chemical signal c action potential = electrical signal Modified from: OpenStax Anatomy and Physiology  Neurons and the Nervous System 2 Synapse: The junction Modified from: OpenStax Anatomy and Physiology between two neurons, where the signal passes from one neuron to the next. In a chemical synapse, the electrical signal (action potential) of the presynaptic neuron will become an electrical signal (action potential) of the post- synaptic neuron, with a chemical signal linking them. The chemical signal (neurotransmitters) crosses the synaptic cleft.  Neurons and the Nervous System 2 The Role of Ca2+ action potential Calcium = electrical signal higher [Ca2+] action potential = electrical signal Modified from: OpenStax Biology 2e  Neurons and the Nervous System 2 The Role of Ca2+ Modified from: OpenStax Biology 2e Action potential reaches Cast ATPase the axon terminal. tosser out cary The action potential (depolarization) causes mm voltage-gated Ca2+ channels open and allow higher [Ca2+] Ca2+ to enter the cell (down ΔCa2+]). The Ca2+ entry causes synaptic vesicles to fuse with the membrane and release neurotransmitter molecules into the synaptic cleft (= exocytosis). (The Ca2+ must be removed shortly afterwards, via a Ca2+- ATPase.)  Neurons and the Nervous System 2 The neurotransmitter Modified from: OpenStax Anatomy diffuses across the synaptic Receptors Specifinity and Physiology cleft and binds to ligand- gated ion channels in the post-synaptic membrane, resulting in a localized depolarization. higher [Ca2+] Post-synaptic neuron has PM receptors for the neurotransmitter always upstream (specificity); -could be on a dendrite or on a cell body → binding of neurotransmitter opens an ion channel → re-start action potential in the post- synaptic neuron  Neurons and the Nervous System 2 Many postsynaptic neurotransmitter receptors are ligand-gated ion channels – the signal for opening is binding of a ligand. Ligand: a molecule that binds to another (usually larger) molecule. In this case, the ligand is the neurotransmitter, and the larger molecule is the ion channel. Binding of the neurotransmitter to the ion channel causes the channel to open. some channel let ioni in some out we'll just say it Binding of the neurotransmitter to the neurotransmitter binding site triggers opening of the ion channel. This is a ligand-gated ion channel. OpenStax Biology 2e  Neurons and the Nervous System 2 Binding of the neurotransmitter to the ion channel on the post-synaptic membrane causes the channel to open; → influx of ions → action potential in the post-synaptic neuron OpenStax Biology 2e  Neurons and the Nervous System 2 However, the ligand is only transiently attached to the ion channel. Afterwards, the neurotransmitter may: 1) be enzymatically degraded into 2) diffuse away from the cleft ed 3) be taken up (“re-uptake”) by the pre-synaptic neuron vesicles It’s important that the signal is not permanent. OpenStax Biology 2e  Neurons and the Nervous System 2 OpenStax Biology 2e Recap about Neurotransmitters: When the presynaptic membrane is depolarized, voltage-gated Ca2+ channels open and allow Ca2+ to enter the cell. The Ca2+ entry causes synaptic vesicles to fuse with the membrane and release neurotransmitter molecules into the synaptic cleft. The neurotransmitter diffuses across the synaptic cleft and binds to ligand-gated ion channels in the post-synaptic membrane, resulting in a localized depolarization; → creates an action potential in the post-synaptic neuron  Neurons and the Nervous System 2 Ca2+ Movement Across the PM at the Synaptic Terminal Ca2+ enters the synaptic terminal via voltage-gated Ca2+ channels; -opening of the channel is due to membrane depolarization (= action potential) -this leads to exocytosis of vesicles containing neurotransmitters This is followed by Ca2+ removal by a Ca2+ pump (= Ca2+-ATPase, = Ca2+-translocating ATPase). There are two Ca2+ transport proteins associated with the axon terminal: 1) the voltage-gated Ca2+ channel allows for Ca2+ entry, and 2) the Ca2+-ATPase removes Ca2+ from the axon. cytosol plasma membrane Higher [Ca2+] ΔADP + Pi - + Lower [Ca2+] Ca2+ ATP 2) Ca2+ pump (Ca2+-ATPase) Ca2+ 1) Voltage-gated Ca2+ channel  Neurons and the Nervous System 2 Brief Summary of How Chemical Synapses Work – Order of Events 1) Action potential reaches the synaptic terminal of the pre- synaptic neuron. 2) This opens voltage-gated Ca2+ channels, allowing Ca2+ to diffuse (down Δ[Ca2+]) into the synaptic terminal. 3) Ca2+ is the signal for exocytosis of synaptic vesicles (containing neurotransmitters), releasing neurotransmitters into the synaptic cleft. 4) Diffusion of neurotransmitters through the synaptic cleft to the post-synaptic neuron.  Neurons and the Nervous System 2 Order of Events (continued) 5) Binding of a neurotransmitter to a ligand-gated ion channel on the post-synaptic neuron leads to opening of the channel and ion diffusion. 6) Channel opening leads to an electrical signal in the post- synaptic neuron. 7) Removal of the neurotransmitter signal in the synaptic cleft (various options). 8) The pre-synaptic neuron needs to pump out the accumulated Ca2+; → Ca2+-ATPase = Ca2+-translocating ATPase  Neurons and the Nervous System 2 Some Diseases and Toxins of the Nervous System Multiple Sclerosis (MS) – due to demyelination of the axons in CNS; → leads to problems with signal transmission Dysautonomia – dysfunction of the autonomic nervous system. Tetrodotoxin – produced by the puffer fish; → inhibition of voltage-gated Na+ channels Anatoxin-a – a cyanobacterial toxin (originally named “Very Fast Death Factor”); -mimics the neurotransmitter acetylcholine, binds to nicotinic acetylcholine receptor of muscles -unlike acetylcholine, anatoxin-a cannot You do not need to understand be degraded neuromuscular junctions. → muscular contraction that never stops Detailed view of a neuromuscular junction: 1.Presynaptic terminal 2.Sarcolemma 3.Synaptic vesicle 4.Nicotinic acetylcholine receptor 5.Mitochondrion CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=305017  Neurons and the Nervous System 2 Bonus Picture By Isaac Oster - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=69565964  Neurons and the Nervous System 2 Another Bonus Picture Resting, Graded and Action Potential https://med.libretexts.org/@go/page/9577  Neurons and the Nervous System 2 Terminology Summary Cell body (= soma) – widest part of the cell; contains the nucleus; can receive signals from synaptic terminals of other neurons Dendrites – can receive signals from synaptic termini of other cells; transmit the signal to the cell body Axon hillock – between the cell body and the axon; works to integrate (sum up) incoming signals and to generate a signal (action potential) if the integrated incoming signals are large enough Axon – the signal travels down the axon, from the axon hillock to the synaptic terminal Synaptic terminal (= axon terminal or terminal button/bouton) – at the end of the axon; contains synaptic vesicles with neurotransmitters; neurotransmitters are released into the synaptic cleft via exocytosis of the vesicles Myelin sheath – a sheath wrapped around the axon; composed of fatty material; the sheath is produced by Schwann cells (peripheral nervous system) or by oligodendrocytes (central nervous system); the cells that produce the sheath are alive (myelinated neurons are found in jawed vertebrates) Nodes of Ranvier – narrow spaces between the Schwann cells or oligodendrocytes on the axon; there is no myelin at the nodes  Neurons and the Nervous System 2 Terminology Summary Synapse - the junction between two neurons, where the signal passes from one neuron to the next. Nervous signal - the signals carried by neurons are electrical signals; more specifically, they are a transient depolarization of the plasma membrane. Electrical synapse - a synapse in which an electrical signal is directly transferred from one neuron to the next; not as common as a chemical synapse. Chemical synapse - a synapse in which the electrical signal of the pre-synaptic cell is transformed into a chemical signal in the synaptic cleft; the chemical signal triggers the formation of an electric signal in the post-synaptic cell; most common type of synapse. Synaptic cleft - narrow space between the synaptic terminal of the pre-synaptic cell and the post-synaptic cell in a chemical synapse; the part of the post-synaptic forming the cleft could be a dendrite or the cell body. Membrane potential – the voltage (or “potential difference”) across the plasma membrane of a cell (all living cells have a membrane potential). Resting potential – the membrane potential across the axon plasma membrane of a neuron when there is no signal being transmitted; the resting potential is typically approximately -70 mV in vertebrates (negative inside the cell relative to positive outside of the cell).  Neurons and the Nervous System 2 Terminology Summary Depolarization – a decrease in the magnitude of the membrane potential from the resting potential; a depolarization means that the difference in electrical charge across the membrane gets smaller, e.g. a decrease to -30 mV from the resting potential of -70 mV is a depolarization. Threshold potential – the minimum depolarization that must occur in order to trigger the large-scale opening of the voltage-gated ion channels; typically approximately -55 mV in vertebrates. Action potential – a transient, large depolarization triggered by the membrane potential exceeding the threshold potential; caused by the large-scale opening of voltage-gated ion channels; the axon potential travels down the axon; may reach +50 to +100 mV. Repolarization – the re-establishment of the resting potential; due to the activity of the Na+/K+-ATPase. Hyperpolarization – the opposite of depolarization; the increase in the magnitude of the voltage across the plasma membrane. Voltage-gated ion channels – ion channels that are open or closed depending on the membrane potential; in axons, the channels are closed when the plasma membrane is at the resting potential; depolarization of the axon plasma membrane causes opening of the channels; like all ion channels, voltage-gated ion channels exhibit specificity; important ion channels in the axon are channels for Na+, K+ and Ca2+.  Neurons and the Nervous System 2 Terminology Summary Neurotransmitter – a chemical released by the pre-synaptic cell by exocytosis of a vesicle of a chemical synapse; the chemical is released into the synaptic cleft and diffuses to a receptor on the post-synaptic cell; there are many types of neurotransmitter, and the different types are detected by specific receptors on the post-synaptic cells. Ligand-gated ion channels – ion channels that open in response to binding of a specific “ligand” (the ligand in this case is a neurotransmitter); found in the plasma membrane of post-synaptic cells, adjacent to the synaptic cleft. Refractory period – a short period of time in which the voltage-gated ion channels do not respond to depolarization; this occurs immediately after an action potential has passed and prevents the backwards transmission of signals up the axon towards the cell body. Central nervous system – brain and spinal cord; among other functions, acts as the integration centre for signals from the peripheral nervous system. Peripheral nervous system – the part of the nervous system that is outside of the central nervous system; sends sensory input to the central nervous system, and receives motor signals from that system. Myelin – a fatty substance contained in living cells that are wrapped around the axon in concentric layers; acts as “electrical insulation”; increases the rate of signal movement down an axon in vertebrates.