NURS 207 (N01) Nervous System Graded & Action Potentials PDF

NURS 207 (N01) Nervous System Generation and propagation of graded and action potential, cell-to-cell communication in the nervous system Nov 18, 2024 Dr. P. Lee  Objectives 1) Describe the electrical signals in a typi...

NURS 207 (N01) Nervous System Generation and propagation of graded and action potential, cell-to-cell communication in the nervous system Nov 18, 2024 Dr. P. Lee  Objectives 1) Describe the electrical signals in a typical neuron 2) Know how graded potentials are formed in the dendritic region of a typical neuron before entering the axon hillock 3) Know how action potential is generated at axon hillock or trigger zone of a neuron 4) Know how action potential is propagated along the axon of a neuron 5) Know how signals are transmitted in the nervous system Electrical signals in neurons  Electrical signals in neurons Neurons are cells with membrane → Membrane potential of a neuron is a direct result of: i) Uneven distribution of ions across the membrane ii) Different membrane permeability of these ions  Electrical signals in neurons The concentration gradient and membrane permeability are involved in forming the electrical signals in neurons ✓ Permeability of an ion through a membrane is a function of the channels that transport this ion ✓ The dynamic of these channels can change by changing the channels’ environmental condition ✓ Most of these channels are gated ion channels i.e. The channels can either open or close in response to stimulus  Gated channels are classified in 3 categories: 1) Mechanically gated ion channels 2) Chemically gated channels 3) Voltage-gated channels  The ease of ions flow through a channel is called the channel’s conductance (G) ✓ Channel opening to allow ion flow is known as “channel activation” ✓ Channel closing even with activating stimulus continues is known as “channel inactivation”  ACh as the ligand that bins to the Ach receptor  When membrane potential changes from -70 to -50 mV  During activation of the channels, the flow of electrical charge carried by an ion is called the ionic current (Iion) ✓ Na+, Cl-, and Ca++ usually flow into the cell (influx) ✓ K+ usually flow out of the cell (K+ efflux) The excitable characteristic of a neuron, created by the activation and inactivation of the gated channels, allows for the generation of nerve impulses (action potentials) which enable the neuron to communicate between various regions of our body and regulation of our body functions Graded potentials  Graded potentials in neurons Graded potentials in neurons are the events of depolarization (excitatory) or hyperpolarization (inhibitory) that normally occur in the dendrites and soma Membrane potential (mV) +40 +20 Membrane potential difference (Vm) 0 −20 Vm decreases Vm −40 increases −60 −80 −100 Depolarization Repolarization Hyperpolarization −120 Time (msec) → Less frequently occurs near the axon terminals Less frequently Usually  Graded potentials in neurons Stimulus hyperpolarization → inhibitory Stimuli can be in the form of: → Chemical depolarization → excitatory e.g.) Neurotransmitters (ligand-gated channels) → Mechanical e.g.) pressure receptor (Mechanically-gated channels)  Graded potentials in neurons ❖ Strength of the stimulus is positively correlated to the amplitude of the graded potential generated i.e. Stronger the stimulus → larger the amplitude of the graded potential ❖ Amplitude of the graded potential is a reflection on the number of gated ion channels are activated (opened), allowing ions to enter (influx) or to leave (efflux) the cell of the stimulated neuron  Graded potentials in neurons For the sensory neurons → Mechanical stimuli or chemical stimuli open gated ion channels in the sensory neurons The ionic flow controlled by the gated channels created the local current flow which is the genesis of the graded potentials Graded potentials may also occurs when an open ion channel become close e.g. When K+ leak channels close (being inhibited as in zebra fish under hypoxic condition), allowing the influx of other +ve ions into the cell and causing a depolarization of the cell  Graded potentials in neurons Amplitude (strength) of graded potential (mV) Distance Distance Stimulus point of origin Stimulus Axon terminal Postsynaptic neuron Na+ Figure 8.7a ESSENTIALS – Graded Potentials Graded potential begins when the stimulus causes the opening of the Na+ gated channels and allows the influx of +ve sodium ions (Na+) spread through the cytoplasm (also known as wave of depolarization or local current flow) V = IR where: V = graded potential I = local current flow R = resistance to current flow  Graded potentials in neurons Amplitude (strength) of graded potential (mV) Distance Distance Stimulus point of origin Stimulus Axon terminal Postsynaptic neuron Na+ Figure 8.7a ESSENTIALS – Graded Potentials The strength of the stimulus determines how many Na+ gated channels will be activated (open) → More Na+ channels open (higher the current), higher the amplitude the graded potential is generate → Higher the amplitude the graded potential (greater voltage), farther the graded potential can spread along the neuron before it dies out (V = IR)  Graded potentials in neurons → If the sum of all the graded potentials is above the threshold at the trigger zone, an electrical signal (action potential) can then be propagated along the axon Subthreshold Graded Potential Suprathreshold Graded Potential Stimulus −40 Stimulus −40 Synaptic −55 −55 T terminal −70 −70 mV Stimulus mV Stimulus Time Time Figure 8.7b ESSENTIALS – Graded Potentials −40 −40 Cell −55 −55 T body −70 mV Sub-threshold −70 mV Threshold Time Time −40 Graded potential −40 Graded potential Trigger below threshold Trigger −55 −55 above threshold T zone zone −70 Axon No action mV Time Action −70 mV Time potential potential → The graded potential fail to trigger an action potential is known as sub-threshold graded potential  Graded potentials in neurons The strength (amplitude) of graded potential will be degraded (decrease in amplitude) along the cytoplasmic space of dendrites and soma because: 1) Current leak → The leak channels along the membrane allow the +ve ions leak out and weaken the current flow inside the cytoplasm 2) Cytoplasmic resistance → Resistance to electrical flow inside the cell  Combination of current leak and cytoplasmic resistance is the reason why graded potential decreases its strength (amplitude) over distance graded potential is generated Graded potentials in neurons Subthreshold Graded Potential Suprathreshold Graded Potential −40 −40 Stimulus Stimulus Synaptic −55 −55 T terminal −70 −70 mV mV Stimulus Stimulus Time Time Figure 8.7b ESSENTIALS – Graded Potentials −40 −40 Cell −55 −55 T body −70 −70 mV mV Time Time −40 Graded potential −40 Graded potential Trigger below threshold above threshold Trigger zone −55 −55 T zone −70 −70 mV mV Axon Further away Time Time Smaller amplitude  Amplitude of the graded potential decreases (due to current leak and cytoplasmic resistance) as it propagated towards the trigger zone located at the junction between the soma and the axon  Sample questions 1) Which part of a neuron is normally receiving information from the neighboring cells? a) axon b) cell body c) dendrites d) axon hillock 2) Which part of a neuron is also known as the trigger zone? a) axon b) cell body c) dendrites d) axon hillock  Sample questions 3) Neurotransmitter is released to the extracellular space from: a) presynaptic axon terminal b) postsynaptic axon terminal c) dendrites d) cell body 4) A depolarizing graded potential: a) makes the membrane more polarized b) makes the membrane less polarized c) occurs when chloride enters the cytosol d) occurs when anion enters the cytosol  Sample questions 5) Depolarization occurs when: a) membrane potential is at its resting membrane potential b) membrane potential is more –ve than the resting membrane potential c) membrane potential is less –ve than the resting membrane potential d) membrane potential is equal to zero 6) Hyperpolarization occurs when: a) membrane potential is at its resting membrane potential b) membrane potential is more –ve than the resting membrane potential c) membrane potential is less –ve than the resting membrane potential d) membrane potential is equal to zero  Answer to sample questions 1) c 2) d 3) a 4) B 5) C 6) B  Generation and propagation of action potential of a typical neuron  Area where graded potentials are generated Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The Presynaptic Synaptic Postsynaptic region where an axon terminal Cell axon terminal cleft dendrite communicates Dendrites body with its postsynaptic target cell Input Integration Output signal signal Subthreshold Graded Potential Suprathreshold Graded Potential Stimulus −40 Stimulus −40 Synaptic −55 −55 T terminal −70 −70 mV Stimulus mV Stimulus Time Time Figure 8.7b ESSENTIALS – Graded Potentials −40 −40 Cell −55 −55 T body −70 mV Sub-threshold −70 mV Threshold Time Time −40 Graded potential −40 Trigger −55 below threshold Trigger −55 Graded potential above threshold T zone zone No action −70 mV Action −70 mV Axon Time Time potential potential  Generation of action potential at the trigger zone If the integrated graded potential causes depolarization at the trigger zone, this graded potential is regarded as excitatory If the integrated graded potential causes hyperpolarization at the trigger zone, this graded potential is regarded as inhibitory Threshold for the generation of an action potential for a typical mammalian neuron is about -55 mV ✓ If the integrated graded potential is equal to or above the threshold, action potential is generated Excitability of cell is referred to its ability to respond to a stimulus and is capable to generate an action potential  Generation of action potential at the trigger zone Trigger zone is usually located at the axon hillock (region located between cell body and axon) for the Sensory Neurons Somatic senses Neurons for efferent neurons and interneurons Dendrites smell and vision Efferent Neurons (multipolar) Trigger zone Dendrites Trigger For the unipolar sensory zone neurons, it is the area immediately adjacent to Schwann cell the sensory receptor Axon where the dendrites join Axon the axon (except for the Axon terminal bipolar neuron → for special senses)  Generation of action potential at the trigger zone The trigger zone is the integrating center of a neuron that contains high density of voltage-gated Na+ channels → If the sum of all the graded potentials has an amplitude (strength) equal to or above the threshold voltage when they reach the trigger zone, voltage-gated Na+ channels at the trigger zone will be activated (channels open) and an action potential will be generated → Transmission of action potential through a neuron is high in speed and great in fidelity  Propagation of action potential along an axon A wave of electrical current passes down the axon. Trigger zone Electrodes have been placed along the axon. Direction of conduction Action potential Membrane potentials potential (mV) recorded simultaneously from each electrode. Membrane Time Simultaneous recordings show that each section of axon is experiencing a different phase of the action potential. Action potentials (spikes) are of uniform strength without any degradation or decay to their amplitudes when propagate along an axon The conduction of an action potential down an axon is similar to energy passed along a series of falling dominos. In this snapshot, each domino is in a different phase of falling. In the axon, each section of membrane is in a different phase of the action potential. Figure 8.8a (1 of 2)  Propagation of action potential along an axon The ability for an action potential to maintain its constant amplitude as it propagates down an axon without decay is due to: → Existing of voltage gated Na+ ion channels in high density within the Node of Ranviers along the axon → As an action potential moves down an axon, it triggers the activation of these voltage gated Na+ ion channels sequentially at the Node of Ranviers The high-speed propagation of an action potential alone an axon is referred to as the conduction of action potential  With high density Also with high Trigger of voltage-gated Nodes of zone density of Na+ channels Ranvier voltage-gated Na+ channels  Propagation of action potential along an axon Action potentials are all-or-none phenomena i.e. An action potential will fire once the threshold is reached → Amplitude of the action potential is the same along the axon regardless the strength of the graded potential if the graded potential is equal to or greater than the threshold Conduction of action potentials down an axon behave like a wave of electrical energy moving along the axon in a constant amplitude Sequence of ionic events for an action potential There are 9 events in the generation an action potential  Sequence of ionic events for an action potential At point #1: The cell is at rest and the membrane potential is equal to the “resting membrane potential” which is maintained by the activity of Na+/K+- ATPase At point #2: Arrival of stimulus in the form of electrical signal causing the depolarization of the membrane (i.e., membrane potential becoming more positive)  Sequence of ionic events for an action potential At point #4: Activation of voltage gated Na+ channels occur after the threshold is reached, allowing massive Na+ influx causing the full depolarization of the membrane (action potential is generated) At point #3: The electrical stimulus has sufficient strength that causes the membrane potential to reach the threshold  Sequence of ionic events for an action potential At point #5: Deactivation of voltage gated Na+ channels (Na+ channels closed and Na+ influx stopped) and voltage gated K+ channels are now opened (K+ efflux occurs) At point #6: During K+ efflux, the membrane potential is returning back to its resting state. A period known as repolarization  Sequence of ionic events for an action potential At point #7: Deactivation of voltage gated K+ channels is not fully accomplished even when membrane potential has already returned back to its resting state (i.e., some K+ efflux is still occurring), causing hyperpolarization of the membrane (a period known as after-hyperpolarization) At point #8: All the voltage gated K+ channels are now closed and Na+/K+- ATPase system is trying to restore the electrochemical gradient back to its equilibrium state Sequence of ionic events for an action potential At point #9: Electrochemical gradient has been restored and membrane potential is returned back to its resting state (resting membrane potential is maintained) Sequence of ionic events for an action potential Depolarization Na+ K+ efflux, influx repolarization Sequence of opening and closing of gates  Speed of propagation for an action potential Speed of action potential in neuron is closely related to the structure of the neuron Myelin sheaths → Myelin sheaths composed of Schwann cells (in PNS) insulate the axon of a neuron Node of Ranvier ▪ Myelin sheaths decrease current leak along the axon ▪ minimizing the decay of the electrical signal → With gap between myelin sheath which is known as node of Ranvier  Speed of propagation for an action potential Speed of action potential in neuron is influenced by: 1) Diameter of axon → Larger the axon’s diameter, faster of the speed of conduction 2) Myelination of the axon → Myelinated axon has a much faster speed of propagation for an action potential → The way of how an action potential propagates along the axon is known as saltatory conduction where action potential appears to jump from one nodes of Ranvier to another  How an action potential is propagated along an axon → High density of voltage-gated Na+ channels are found within the membrane at the trigger zone and nodes of Ranvier of a neuron → Unlike the graded potential, the action potential moving alone the myelinated axon will has minimal decay: a) Insulation by the myelin sheath which prevents current leak through the membrane b) Length of nodes of Ranvier is so short that voltage drop due to cytoplasmic resistance is very minimal → When the impulse (with minimal decay due to the myelin sheath) reaches the node of Ranvier, its voltage is always much higher than that of the threshold to activate the voltage-gated Na+ channel located at node of Ranvier → A new action potential with the same amplitude as the one from before (from the previous node of Ranvier) is generated A wave of electrical current passes down the axon. Trigger zone Electrodes have been placed along the axon. potential (mV) Direction of conduction Action potential Membrane potentials Membrane recorded simultaneously from each electrode. Time Simultaneous recordings show that each section of axon is experiencing a different phase of the action potential. How an action potential is propagated along an axon SALTATORY CONDUCTION Node Node Myelin sheath Node of Ranvier Na+ Depolarization Degenerated myelin sheath Na+ Current leak slows conduction Figure 8.16 In demyelinating diseases, conduction will either be slow or absence (current leaks out of the damaged regions between the node of Ranvier)  Neural communication and how signals are transmitted between cells in the nervous system  Neural communication at synapses Neuron #1 Communication Neuron #2 Junctions (synapses) Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The region where an Presynaptic Synaptic Postsynaptic axon terminal axon terminal cleft dendrite communicates Cell with its Dendrites body postsynaptic target cell Input Integration Output signal signal  Synaptic junction between a neuron and the target cell 2 main components in a synapse: 1) Presynaptic axon terminal → Adjacent to the cell membrane at either the dendrites (axodendritic) or cell body (axosomatic) of the postsynaptic neuron → Can also be next to the postsynaptic cell membrane of a non-neuronal cell (e.g. motor unit of a muscle) 2) Postsynaptic cell membrane → Can either be neuron or non-neuron → Pre and postsynaptic membrane are usually separated by the synaptic cleft (chemical synapses) 2 main types of synapse: Electrical & chemical electrical synapse chemical synapse (gap junction) (neural transmitter) Neural transmitter Gap junction e.g.) Signal conduction e.g.) Innervation of motor between myocytes in the unit in skeletal muscle by heart uses gap junction the somatic motor neuron 2 main types of synapse: 1) Electrical synapse → Structural connection known as gap junction that forms a conductive link containing connexon connexon channels channels → Each gap junction contains hundred or so connexons → With low electrical resistance to electronic current flow and allow signals transmission with minimal attenuation or delay → Ionic currents can flow easily across the membrane barriers from the presynaptic cell into the postsynaptic cell through the connexon pores  Advantages of having electrical synapses i) Faster communication ✓ Faster than using chemical synapses ii) Synchronization ✓ A single stimulus can activate a group of neurons in unison in the fastest possible response → usually defensive in nature 2) Chemical synapse → Use neurotransmitters to provide electrical continuity between adjacent cells → Majority of the neural synapses are the chemical synapses ✓ Electrical signal of the presynaptic cells is converted into neurocrine (chemical signal in a form of neurotransmitter secreted by the neuron) that cross the synaptic cleft and binds to receptors on its target cell to elicit a response  Neurotransmitters Neurocrines (secreted by neurons) that bind to neurotransmitter receptors located in the target cells including either the postsynaptic neurons (usually at the dendritic regions), muscle (neuromuscular junction/motor end-plate), or glands → There are vast number of chemical messengers → Binding of these chemical messengers to the receptors in the membrane can either: ✓ Induce the opening or closing the ion channels thereby changing the membrane potential rapidly ✓ Or act slowly via second messenger systems that affects the chemical reaction inside the cells  Neurotransmitters Some of the well-known neurotransmitters are: 1) Acetylcholine (ACh) ✓ Released by various PNS and CNS neurons ✓ Can be an excitatory or inhibitory neurotransmitter ✓ Closely associated with the parasympathetic neurons  Neurotransmitters 2) Amino acids ✓ Some amino acids are neurotransmitters in CNS  Examples such as glutamate and aspartate ▪ Both have strong excitatory effects  Another important neurotransmitters are gamma-aminobutyric acid (GABA) and glycine ▪ GABA affects mostly the CNS (the brain in particular) ▪ As the common inhibitory neurotransmitters in CNS ▪ Binding of glycine (mainly in the spinal cord) to the receptors also has the same inhibitory effect  Neurotransmitters 3) Biogenic amines ✓ Formed when the carboxyl group in amino acids are removed (decarboxylated)  Examples such as norepinephrine, epinephrine, dopamine, and serotonin ▪ Mostly affecting the CNS (norepinephrine affect the sympathetic nervous system within the ANS) ▪ Biogenic amines can either excitatory or inhibitory ▪ Norepinephrine, epinephrine, and dopamine are also referred to as catecholamines  Neurotransmitters 3) Biogenic amines ▪ Norepinephrine can be classified as neurotransmitters when released by neural axonal terminals, or as hormones when released by the adrenal medulla (inner portion) of the adrenal gland (located just above the kidneys) ▪ Dopamine (DA) are related to emotional and addictive responses, as well as the sensation of pleasure (reward center) ▪ Serotonin are involved in many areas such as sensory perception, temperature regulation, mood control, and appetite, etc.  Neurotransmitters 4) Adenosine triphosphate (ATP) and the associated purines ▪ Purine ring is the adenosine portion of the ATP ▪ Purines include adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) ▪ As the excitatory neurotransmitters in both the CNS and PNS  Neurotransmitters 5) Nitric oxide (NO) and carbon monoxide (CO) ▪ Known as gasotransmitters ▪ NO release causes vasodilation (relaxation of the smooth muscles) ▪ CO is an excitatory neurotransmitter and with the physiological function of anti-inflammatory and vasodilation  Neurotransmitters 6) Neuropeptides ▪ Neurotransmitters with chain of amino acids linked together by peptide bonds (bond between carbon and nitrogen of two amino acids) ▪ Widespread in CNS and PNS ▪ Endorphins is one of the well-known neuropeptides which also refer to as opioid peptides → Function as the body’s endogenous painkillers  Sample questions 1) Once the threshold is reached, action potential generated along a normal myelinated axon is: a) Uniform in strength that travels to the end of axon b) All-or-none phenomena c) The same amplitude regardless the strength of the graded potential d) All the above 2) Generation of an action potential in a neuron is usually accomplished by: a) Activation of the voltage gated Na+ channels b) Activation of the voltage gated K+ channels c) Activation of the voltage gated Cl- channels d) Activation of the voltage gated Ca2+ channels  Sample questions 3) Repolarization of an action potential is usually accomplished by: a) Activation of the voltage gated Na+ channels b) Activation of the voltage gated K+ channels c) Activation of the voltage gated Cl- channels d) Activation of the voltage gated Ca2+ channels 4) Absolute refractory period is defined as: a) No AP can be generated regardless how strong the stimulus is b) No activation of the gated K+ channels can occur c) No activation of the gated Cl- channels can occur d) Activation of the voltage gated Na+ channels will occur  Sample questions 5) Gated channels can be activated: a) Mechanically b) Chemically c) Electrically d) All the above 6) Membrane potential of a neuron is a direct result of: a) Uneven distribution of ions across the membrane b) Different membrane permeability of ions c) All the anions are located intracellularly d) a and b are both correct  Sample questions 7) Faster communication and synchronization are two advantages of: a) Chemical synapses b) Electrical synapses  Answer to sample questions 1) d 2) a 3) b 4) a 5) d 6) d 7) b