Physiology - Action Potential and Nerve Physiology PDF

PHYSIOLOGY ACTION POTENTIAL AND NERVE PHYSIOLOGY UNIVERSITY OF SANTO TOMAS - FACULTY OF MEDICINE AND SURGERY UNIT 2 | SHIFT 1 | TERM 1 | A.Y. 2023-2024 | Lecturer: Dr. Elaine C. Cunanan...

PHYSIOLOGY ACTION POTENTIAL AND NERVE PHYSIOLOGY UNIVERSITY OF SANTO TOMAS - FACULTY OF MEDICINE AND SURGERY UNIT 2 | SHIFT 1 | TERM 1 | A.Y. 2023-2024 | Lecturer: Dr. Elaine C. Cunanan or neighboring cell that causes the release of UNIT 02 | ACTION POTENTIAL AND NERVE chemical messengers (neurotransmitters) to PHYSIOLOGY communicate with other cells ➔ Most neurons contain a cell body and two types of processes - dendrites and axons TABLE OF CONTENTS 1. Functional Anatomy of the Neuron 1.1. Parts of the Neuron C01.1. PARTS OF THE NEURON (L.Y.E.C.) 1.2. Axonal Transport ➔ Cell Body or Soma - contains the nucleus 2. Potentials (genetic information) and ribosomes (machinery 2.1. Electrochemical Potential Difference for protein synthesis) 2.2. Equilibrium Potential ➔ Processes - connect neuron to neuron 3. Resting Membrane Potential ◆ Dendrite - receive signals from other 3.1. Nernst Equation neurons; shorter than axons 3.2. Goldman-Hodgkin-Katz Equation ○ From the Greek word 3.3. Membrane Potential States “dendron” which 4. Graded Potential means tree, the part 4.1. Types of Graded Potential resembling that of trees’ 4.2. Properties of Graded Potential branches. 4.3. Passive Responses and Local Dendritic spines - knoblike Responses outgrowths; branching increases 5. Action Potential the cell’s surface area further. 5.1. Classification of Stimuli ◆ Axon or Nerve Fiber - sends signals to 5.2. Voltage-Gated Ion Channels other neurons; longer than dendrites. 5.3. Phases/Ion Channel States ○ From the Greek word 5.4. Refractory Period “axon”, which means 6. Basis of Nerve Excitability “axis”, resembling a 6.1. Threshold Potential Negativity shaft or a vertical axis of 6.2. Resting Membrane Potential a neuron. Negativity Axon Hillock or Initial 7. Synaptic Transmission Segment - connects axon to 7.1. Synapse body (soma); trigger zone; 7.2. Types of Synaptic Transmissions where electrical signals (action 7.3. Presynaptic Vesicle Fusion potentials) are generated for 7.4. Postsynaptic Potentials propagation. 7.5. Types of Summation Collaterals - branches of the 8. Nerve Conduction Velocity axon; the greater degree of 8.1. Myelin Sheath of Axons axon and axon collaterals, the 8.2. Saltatory Conduction greater is the cell’s sphere of 9. Chapter Summary influence. 10. References Axon Terminal - end of a neuron; responsible for releasing neurotransmitters from the axon. C01. FUNCTIONAL ANATOMY OF THE NEURON (L.Y.E.C.) (P.A.P.B.) Associated ion channels: Overview (L.Y.E.C.) ➔ Cell body and dendrites contain ligand-gated ➔ Neuron - functional unit of the nervous system; ion channels operates by generating electrical signals from one part of the cell to another part of the same LEAPMED ‘25 1 PHYSIOLOGY - Action Potential and Nerve Physiology ➔ Axons have high concentration of voltage-gated ion channels (between nodes of Ranvier, allowing saltatory conduction) ➔ Axon terminals contain voltage-gated calcium channels Figure 01.2 - 1 : Axonal transport using kinesin and dynein in a motor neuron. C02. POTENTIALS (G.S.C.) (P.A.P.B.) Principles of Electricity and Charges (Overview) (G.S.C.) ➔ Ions ◆ Atoms who have lost or gained electrons, forming an ionic charge ➔ Ionic charge ◆ Ions can either be positive or negative (positive charge due to loss of electrons; negative charge due to gaining electrons) Figure 0.1 - 1 : Structure of a neuron. ➔ Current ◆ Flow of electrical charge (ions) from one C01.2. AXONAL TRANSPORT (L.Y.E.C.) point to another ➔ Potential ➔ Axonal Transport - transport of substances ◆ The capability of ions to do work or to synthesized in the neuron to the nerve endings move due to their potential difference through the cytoskeleton. ➔ Electric Potential Difference/Potential ➔ With motor proteins, substances can move Difference through the neuron ◆ Refers to the difference between ◆ Kinesin - responsible for anterograde charges of ions (positive and negative) movement (soma to terminal) ◆ Ions with opposite charges attract, ◆ Dynein - responsible for retrograde causing an electrical driving force that movement (terminal to soma) causes ions to move towards each other (cause of a current) LEAPMED ‘25 2 PHYSIOLOGY - Action Potential and Nerve Physiology ➔ Membrane potential ◆ In a cellular context, a potential allows ions to move in between the extracellular and intracellular lining of the cell/plasma membrane ◆ Made possible by electrical and chemical potential difference/gradients (electrochemical gradient/potential difference) Figure 02.1 - 2 : The intracellular and extracellular driving forces C02.1. ELECTROCHEMICAL POTENTIAL C02.2. EQUILIBRIUM POTENTIAL (G.S.C) DIFFERENCE (G.S.C) ➔ Diffusion Potential ➔ Electrical potential (Electrical Gradient) ◆ This is the potential difference of ions ◆ Electrical driving force due to attraction after they diffuse from one side of the between opposite charges among ions membrane to the other side of the ◆ A cell’s intracellular potential is more membrane due to the chemical gradient negative than the external surface (from high to low concentration) ➔ Equilibrium Potential ◆ The movement/diffusion of ions stops when this is achieved. ◆ Electric potential of an ion that balances the chemical potential from its opposite direction Example: Given that potassium has an equilibrium potential of -94mV. When the diffusion Figure 02.1 - 1 : The intracellular and extracellular potential that pushes them from charges and their respective driving forces inside to outside reaches -90mv, there will no longer be any ➔ Chemical potential (Chemical Gradient) movement because the ◆ Chemical driving force due to the chemical gradient that pushes diffusion of ions from a relatively high them from outside to inside concentration to low concentration would be negated Example: Sodium diffuses Example Relationship between Diffusion and through the membrane from Equilibrium Potential: outside to inside the cell ➔ As ions keep on diffusing from outside to inside because it has a higher of the membrane, diffusion potential eventually concentration outside the cell reaches the ion’s equilibrium potential that terminates the outside to inside movement of the ion C03. RESTING MEMBRANE POTENTIAL (M.Y.H.V., G.S.C.) (P.A.P.B.) Overview (M.Y.H.V.) ➔ Resting Membrane Potential (RMP) LEAPMED ‘25 3 PHYSIOLOGY - Action Potential and Nerve Physiology ◆ Electrical potential difference across the ◆ Resulting net flux of the ion would be 0 cell membrane in resting state – “neuron ◆ The greater the concentration ratio of is not sending any signal” an ion is (ratio between the intracellular ◆ In this state, opposite electrical charges and extracellular ion concentrations), exist on either side of the cell membrane the greater the concentration ◆ Charge inside is more negative than potential (possibility of ion diffusion outside from one side to another) there is, the ➔ Concentrations In and Out of the Cell greater Nernst potential is needed to ◆ Sodium (Na+) and chlorine (Cl-) have negate that concentration potential to higher concentrations outside the cell achieve net flux of 0 ◆ Potassium (K+) and amino acids (A-) have higher concentrations inside the ➔ Nernst Equation cell ◆ Used to compute the equilibrium ◆ Calcium (Ca2+) has higher potential needed to stop ion flux or the concentration outside the cell Nernst potential (Veq) ◆ Electrical potential needed to balance *Remember through this the opposing force (chemical potential/gradient) ◆ Equilibrium potential varies from ion to ion ◆ The membrane potential (total potential along the membrane) would be equal to the Equilibrium potential of a specific ion, if that specific ion is the only type of ion present Figure 03.1 - 1 : The Nernst Equation, wherein: Figure 03 - 1 : Mnemonics for the intra and ➔ Veq – equilibrium potential (Nernst potential) extracellular charges of a cell ➔ R – universal gas constant (8.314 J K-1 mol-1) ➔ T – temperature in Kelvin (T (in °C) + 273.15 K) ➔ z – valence of the ion SCCOUT → Sodium, Chlorine, Calcium ➔ F – Faraday’s constant (96485 C mol-1) OUTside ➔ [C]o – ion’s extracellular concentration ➔ [C]i – ion’s intracellular concentration PAIN → Potassium, Amino acids INside Table 03.1 - 1 : Current voltage relationship of a hypothetical cell containing Na, K, Cl selective channels C03.1 NERNST EQUATION (M.Y.H.V., G.S.C.) EC IC Nernst ➔ Nernst Potential concentration concentration Potential ◆ Diffusion potential needed to be reached (in mEq/L) (in mEq/L) Ei (in mV) in order to oppose/balance/negate the Na+ 142 14 +61 net potential of an ion that allows ion flux from one side of the membrane to K+ 4 140 -94 another LEAPMED ‘25 4 PHYSIOLOGY - Action Potential and Nerve Physiology Cl- 105 30 -33 C03.2. GOLDMAN-HODGKIN-KATZ EQUATION (M.Y.H.V., G.S.C.) C03.3 MEMBRANE POTENTIAL STATES (G.S.C., M.Y.H.V.) ➔ Goldman-Hodgkin-Katz Equation ◆ “Expanded Nernst Equation” C03.3.1. POLARITY (G.S.C.) ◆ Used for computing the net equilibrium potential along the membrane, ➔ Polarity considering all present ions ◆ Separation of charges between two ◆ Ions present usually falls among these ends, one end being more negative than three: Na+, K+, and Cl- the other These 3 ions are the most ◆ Example: At RMP, the intracellular important ions for membrane potential polarized, while the development of neuronal and extracellular membrane potential is not muscular cells. Polarized cell - having a more ◆ As would be seen in the Goldman negative intracellular space, equation, the expanded equation takes indicating a resting state into account the following: Concentrations ( C) inside and C03.3.2. MAJOR CONTRIBUTORS FOR EACH ION outside the cell (Co and Ci) (M.Y.H.V., G.S.C.) Permeability of each ion to the membrane (P) 1. Ion Concentration Gradient Each ion’s charge polarity a. Potassium has the highest (valence; + or -) concentration gradient 2. Ion Membrane Permeability a. At RMP the only channels open are the leaky channels. Therefore, permeability of ions is only determined by the amount of leaky channels present to allow ion passage across the membrane Figure 03.2 - 1: The Goldman-Hodgkin-Katz Equation b. With this, potassium ions are the most permeable at RMP because these ions ➔ Concentration Gradient can cross through the potassium leaky ◆ Difference between the concentration channels present inside and outside or outside and inside 3. Polarity/Valence ➔ Ion Permeability a. The negativity within the cell and the ◆ Permeability varies directly with the equilibrium outside the cell at RMP is number of non-gated, open ion channels because of the dominance or balancing at rest (“leaky” channels) of ionic charges respectively. These are More leaky channels → Higher the positive charges of potassium and permeability sodium; and the negative charge of ◆ Potassium has the highest chloride ions concentration gradient and permeability 4. Na+-K+ ATPase pump [(-) 4 mV] Hence, potassium is the major a. Pumps 3 Na+ out and 2 K+ in ion that affects RMP. i. Contributes about (-) 4 mV b. Maintains the negativity within the membrane and the concentration gradient that is disrupted by continuous LEAPMED ‘25 5 PHYSIOLOGY - Action Potential and Nerve Physiology leak of ions from the open “leaky” ➔ Local ion current flows / propagates to adjacent channels region to trigger a change in MP c. Called an “electrogenic pump” C03.3.3 PHASES OF CHANGE IN MEMBRANE POTENTIAL (M.Y.H.V.) ➔ Depolarization ◆ From RMP, the membrane becomes less negative (e.g. from -70 mV to -60 mV) and the potential decreases Result of Na+ channels opening ➔ Repolarization Figure 04 - 1 : Graphical representation of Graded ◆ Return to RMP; membrane becomes Potential in terms of Time and Stimuli Applied more negative again ◆ Only occurs if preceded by a C04.1. TYPES OF GRADED POTENTIAL (B. A. S. B) depolarization phase ➔ Hyperpolarization ➔ Less negative (depolarizing) ◆ From RMP, the membrane becomes ◆ The potential becomes less negative more negative (e.g. from -70 mV to -80 ◆ Example: From -70 RMP to -40 RMP mV) and potential increases ➔ More negative (hyperpolarizing) result of K+ channels opening ◆ The potential becomes more negative ◆ Example: From -70 RMP to -100 RMP Figure 04.1 - 1 : Graphical representation of Depolarizing vs. Hyperpolarizing Graded Potential C04.2. PROPERTIES OF GRADED POTENTIAL (L.Y. E.C) Figure 03.3.3 - 1: Graphical representation of the changes in membrane potential ➔ The most important properties of a graded potential are: ◆ Does not have a refractory period C04. GRADED POTENTIAL (B. A. S. B., L.Y. E.C) ◆ Decremental (F. M. L. P) Inverse relationship - Change in Overview (B. A. S. B) membrane potential decreases ➔ Relatively small magnitude changes in as distance from site of origin membrane potential (MP) increases ➔ Mainly occur in postsynaptic dendrites or cell Due to leakage of charge along membrane = reduces local bodies; rare in axons current further along the ➔ Greater intensity = Greater change (magnitude membrane = magnitude and duration) in MP LEAPMED ‘25 6  PHYSIOLOGY - Action Potential and Nerve Physiology diminishes with increasing Conduction Decremental Non-decremental distance ◆ Bidirectional General Dendrites, cell Axon (axon ◆ Can be summated (See C07.5. Types location soma (rarely axon) hillock to axon of Summation) terminal) ◆ Magnitude of graded potential varies directly with the magnitude of the Direction Bidirectional Unidirectional triggering event (stimulus) (Propagation) ➔ Stimuli for gated ion channels to open: ◆ Chemical - ligand (neurotransmitter) ◆ Mechanical - pressure C04.3. PASSIVE RESPONSES AND LOCAL ◆ Electrical - change in membrane RESPONSES (L.Y. E.C) (B. A. S. B) voltage (rare) ➔ Passive Response (Electronic Conduction) ◆ Passive flow of a charge in electric Table 04.2 - 1: Properties of Graded Potential and Action Potential (Adapted from PhysiologyWeb and Dr. potential along a nerve or muscle Cunanan’s Lecture PPT.) membrane ➔ Local Responses: Property/ Graded Potential Action Potential ◆ Postsynaptic potential (Neuron) Characteristic ◆ Endplate potential Polarity Can be depolarizing Always leads to ◆ Receptor or generator potential (EPSP) or depolarization ◆ Pacemaker potential hyperpolarizing ◆ Slow-wave potential (IPSP) *To produce graded potentials, gated ion channels open (See C07.4. once activated by different stimuli Postsynaptic Potentials) Table 04.3 - 1: Stimuli for Gated Ion Channels to Open Magnitude Proportional to the All or none Type of Type of Ion Type of Ion strength of the Stimuli Channel Activated Channel stimulus (greater Stimuli Activated stimulus, more Stimuli frequent) Refractory N/A Has Absolute and Chemical Chemically-gated Ligand Period Relative (neurotransmitter) Refractory Periods Mechanical Mechanically-gated Pressure Involved Ion Various Only Electrical Voltage-gated Change in Channels (ligand-gated, voltage-gated membrane mechanically-gated, Na+ and potential (voltage) but rarely voltage-gated K+ voltage-gated) channels C05. ACTION POTENTIAL (L.Y.E.C., G.S.C., Involved Ions Na+, K+, or Cl− Na+ and K+ M.Y.H.V., B. A. S. B.) (J.G.A.C.) Overview (G.S.C.) Summation Can be over time N/A ➔ Also called the spike or firing potential (temporal ➔ A rapid change in membrane potential from summation) or resting to active across space ➔ ALL OR NONE phenomena, where the action (spatial summation) potential will only start once a specific amount of membrane potential is reached (threshold) LEAPMED ‘25 7 PHYSIOLOGY - Action Potential and Nerve Physiology ➔ Regardless of how strong the stimuli is, as long C05.2. VOLTAGE-GATED ION CHANNELS (L.Y.E.C.) as the threshold is reached the magnitude of the ➔ Action potentials causes membrane action potential is constant depolarization through the opening and closing ➔ Triggered through the involvement of of voltage-gated ion channels voltage-gated sodium and potassium ◆ Depolarization - rapid influx of Na+ ions channels followed by a slightly slower efflux of K+ ➔ Conduction: Non-decremental ions ➔ Propagation: Unidirectional ➔ AP associated with Na+ voltage-gated ion channel and K+ voltage-gated ion channel ◆ Higher concentration in area below axon C05.1. CLASSIFICATION OF STIMULI (B. A. S. B) hillock, especially along the axon (where AP is propagated) Voltage-gated Na+ channel ➔ Has two gates ◆ Activation gate - looks like inverted L ◆ Inactivation gate - looks like upright L “Outer” sounds like it starts with “A,” so Activation gate. Inactivation gate=inner side. Figure 05.1 - 1: Stimulus intensity above threshold and AP frequency Table 05.1 - 1: Classification of Stimuli and their Characteristics Type of Intensity Triggers Action Stimulus Potential (Yes/No) Subthreshold Weak No Figure 05.2 - 1: Voltage-gated Na+ channel states from Stimulus depolarization Dr. Cunanan’s PPT. (graded potential) ➔ Resting - activation gate closed, inactivation gate open Threshold Lowest intensity Yes ◆ Membrane is polarized Stimulus that will trigger ➔ Activated - activation and inactivation gates AP open ◆ Membrane undergoes depolarization Suprathreshol Higher intensity Yes ➔ Inactivated - activation gate open, inactivation d Stimulus (same gate closed magnitude, ◆ Membrane undergoes repolarization (no more frequent) more sodium can enter the cell) ➔ Magnitude of the APs produced are the SAME Table 05.2 - 1: Summary of Voltage-gated Na+ channel (independent of intensity above threshold) states ➔ CNS deciphers the intensity of the stimulus by Na+ Ion Channel Resting Activated Inactivated the frequency of APs transmitted ➔ Stronger stimulus = higher frequency of Activation Gate Closed Open Open generated APs Inactivation Gate Open Open Closed LEAPMED ‘25 8 PHYSIOLOGY - Action Potential and Nerve Physiology C05.3.1. PROCESS (L.Y.E.C.) Voltage-gated K+ channel ➔ An action potential is fired when the threshold ➔ Only has one gate found on the inner surface of (-55mV) stimulation is reached. the cell membrane ➔ The membrane is polarized (-70mV) during RMP, and it must reach -55mV to generate an AP. ➔ This will occur at the axon hillock, the trigger zone. Figure 05.2 - 2: Voltage-gated Na+ channel states from Dr. Cunanan’s PPT. ➔ Resting - activation gate is closed ◆ Membrane is polarized ➔ Slow activation - activation gate is open ◆ Repolarization - K+ ion channel is slow to open, allowing the K+ ions to flow back inside the cell (back to more negative inside) ◆ Hyperpolarization - K+ ion channel is also slow to close; even more negative inside due to excess open potassium channels and potassium efflux Figure 05.3.1 - 1: Graph of membrane potential during an action potential. C05.3. PHASES/ION CHANNEL STATES (L.Y.E.C., G.S.C., M.Y.H.V., B. A. S. B.) 1. DEPOLARIZATION (initial upstroke) - from RMP (-70mV) to 0mV mark a. Membrane suddenly becomes permeable to Na+, hence many voltage-gated Na+ channels are open b. Causes rapid influx of Na+ ions inside the cell, making the interior less negative c. Na+ has highest permeability/conductance at this stage due to opening of voltage-gated Na+ channels Figure 05.3 - 1: Phases of Nerve Action Potential 2. OVERSHOOT - from 0mV to +30mV mark a. Still a part of depolarization Mnemonic for Nerve Action Potential Phases: DORA b. Due to great excess of Na+ flowing D - Depolarization inside, membrane potential overshoots 📖 O - Overshoot to beyond 0mV R - Repolarization i. In smaller fibers and CNS neurons, A - Afterhyperpolarization the potential only approaches zero level and does not overshoot to the positive state LEAPMED ‘25 9 PHYSIOLOGY - Action Potential and Nerve Physiology c. Na+ still has highest permeability/conductance (part of C05.3.2. STATES OF VOLTAGE-GATED ION depolarization) CHANNELS THROUGH STAGES OF AP (L.Y.E.C., G.S.C., M.Y.H.V.) 3. REPOLARIZATION (downward stroke) - goes back to RMP (-70mV) C05.3.2.1. AT RMP (G.S.C.) a. Voltage-gated Na+ channels begin to close b. Voltage-gated K+ channels start opening more c. K+ has highest permeability/conductance at this stage 4. AFTERHYPERPOLARIZATION (undershoot) a. Still a part of repolarization b. Membrane becomes more negative than RMP due to the slow closing of voltage-gated K+ channels c. Undershoot will eventually revert to RMP of -70mV d. K+ still has highest permeability/conductance (part of repolarization) Figure 05.3.2.1 - 1: State of voltage-gated Na+ and K+ channels during RMP phase. ➔ Sodium and potassium leaky channels are always open C05.3.2.2. PHASES 1 AND 2 (DEPOLARIZATION AND OVERSHOOT) (M.Y.H.V.) Figure 05.3.1. - 2: Diagram of the action potential process from BioNinja. LEAPMED ‘25 10 PHYSIOLOGY - Action Potential and Nerve Physiology Figure 05.3.2.2 - 1: State of voltage-gated Na+ and K+ C05.3.2.4. PHASE 4 (HYPERPOLARIZATION AND channels during depolarization and overshoot phase. UNDERSHOOT OR AFTERHYPERPOLARIZATION) (M.Y.H.V.) ➔ At threshold (-55 mV), both voltage-gated Na+ and K+ channels are triggered ➔ Activation gates of Na+ channels open quickly Table 05.3.2.4 - 1: State of voltage-gated Na+ and K+ leading to an influx of sodium channels during afterhyperpolarization phase. ◆ Results in depolarization and overshoot ➔ More voltage-gated Na+ channels open by positive feedback ➔ Voltage-gated K+ channels are triggered but are not open (hence K+ gate is closed) ➔ Leaky Na+ and K+ channels are still open (always open) C05.3.2.3. PHASE 3 (REPOLARIZATION) (L.Y.E.C.) ➔ Caused by the slow closing of voltage-gated K+ channel activation gate resulting in a more negative membrane potential than RMP ➔ At the latter third of repolarization to afterhyperpolarization, some voltage-gated Na+ channels are back to their resting state ◆ “Some” because the rate at which channels go back to their resting state varies ➔ MP is brought back to RMP by the Na+ - K+ ATPase pump (3 Na+ out 2 K+ in) C05.4. REFRACTORY PERIOD (G.S.C.) Purpose ➔ Allows the membrane potential to return at its resting state ➔ To assure a unidirectional flow of impulse Figure 05.3.2.3 - 1: State of voltage-gated Na+ and K+ ➔ To limit the frequency of Action potential channels during repolarization phase. (prevents multiple impulses to flow along the nerve fiber simultaneously; overlapping) ➔ Important especially in the heart to prevent ➔ Repolarization begins at peak membrane cardiac arrest potential (+30mV) ➔ Voltage-gated Na+ channels become inactivated Absolute Refractory Period (no more Na+ can enter the cell): ➔ From the moment action potential begins, up to ◆ Voltage-gated Na+ channel activation the first ⅔ of the repolarization stage (from gate is open activation until opening of voltage-gated ◆ Voltage-gated Na+ channel inactivation potassium channels) gate is closed ➔ Does not allow another stimulus to trigger an ➔ Voltage-gated K+ channel begin to slowly open action potential, only during this time (delayed slow opening) ➔ Because sodium channels are still either ➔ Leaky Na+ and K+ channels are open (all the inactivated or activated at this stage (remember time) that an action potential only begins when all LEAPMED ‘25 11 PHYSIOLOGY - Action Potential and Nerve Physiology voltage-gated ion channels and the membrane ➔ Blood potassium levels can influence RMP and potential are at rest) can therefore affect excitability Relative Refractory Period ➔ From the latter ⅓ of the repolarization stage up to the afterhyperpolarization stage (around the time potassium channels close) ➔ An AP can now be triggered by a higher than threshold stimulus since some Na+ channels are already at rest Figure 06.1 - 2: Relationship between Resting C06. BASIS OF NERVE EXCITABILITY (G.S.C., Membrane Potential and Excitability M.Y.H.V.) (J.G.A.C.) C07. SYNAPTIC TRANSMISSION (L.Y. E.C., M. Y. H. C06.1. THRESHOLD POTENTIAL NEGATIVITY V., B. A. S. B) (F. M. L. P) (G.S.C.) C07.1. SYNAPSE ➔ The negativity of a threshold potential can Overview (M. Y. H. V) directly affect nerve excitability ➔ Synapse ◆ Triggering an action potential ◆ Junction between two neurons where (excitability) has a higher chance if the one neuron alters the activity of another threshold can easily be reached from neuron RMP (if threshold potential value is near ◆ Also described as the “space between the RMP value) two neurons” ◆ More negative TP (nearer to RMP) → ◆ Information is transmitted from the axon higher chance of nerve excitability terminals of the first neuron (presynaptic ◆ Less negative TP (farther from RMP) → neuron) to the soma or dendrites of the lower chance of nerve excitability second neuron (postsynaptic neuron) ➔ Blood calcium levels can influence TP and can ◆ Determines the directions that the therefore affect excitability nervous signals will spread through the nervous system ◆ Facilitatory and inhibitory signals can control synaptic transmission ◆ Selective action: allows strong signals to pass, amplifies weak signals Figure 06.1 - 1: Relationship between Threshold Potential and Excitability C06.2. RESTING MEMBRANE POTENTIAL NEGATIVITY (M.Y.H.V.) ➔ RMP negativity inversely affects nerve excitability. ◆ More negative RMP (farther from TP) → lower chance of nerve excitability ◆ Less negative RMP (nearer to TP) → higher chance of nerve excitability LEAPMED ‘25 12 PHYSIOLOGY - Action Potential and Nerve Physiology C07.1.1. TWO TYPES OF NEURONS (L.Y. E.C) C07.2. TYPES OF SYNAPTIC TRANSMISSIONS (B. A. S. B) ➔ Electrical Synapse (Connexons) ◆ Connexons - gap junctions that connect the presynaptic and postsynaptic neurons Does NOT contain gates, always open ◆ Connexons serve as a channels for the direct transfer of ionic current from presynaptic neurons to postsynaptic neurons Uncommon; more prominent in the GI tract and pacemakers Required for simultaneous action potential generation in Figure 07.1 - 1. Relation of presynaptic neuron and rhythmic contractions postsynaptic neuron. ◆ Transmits action potentials from one ➔ Presynaptic neuron smooth muscle to next visceral smooth ◆ Sends signals toward the synapse muscle ◆ Axon terminal adjacent to the synapse ◆ Communication is extremely rapid but ◆ Communicates with second or not versatile (rare in the nervous neighboring neurons using chemical system) messengers (neurotransmitters) ➔ Postsynaptic neuron ◆ Sends signals away from the synapse ◆ Dendrite or soma adjacent to the synapse ◆ Receives neurotransmitters through ligand-gated ion channels (Na+, K+, or Cl- depending on the area) C07.1. 1. 2 TYPES OF PRESYNAPTIC NEURONS (L.Y. E.C) ➔ Excitatory ◆ Secretes a neurotransmitter that excites the postsynaptic neuron ◆ Common excitatory neurotransmitters: Figure 07.2 - 1: Electrical Synapse Glutamate Aspartate ➔ Chemical Synapse (Synaptic Cleft) ➔ Inhibitory ◆ Most common in the nervous system for ◆ Secretes a neurotransmitter that inhibits transmitting signals the postsynaptic neuron ◆ Presynaptic neuron releases a ◆ Common inhibitory neurotransmitters: neurotransmitter that will act on a Glycine receptor protein in the postsynaptic Gamma Aminobutyric Acid neuron (GABA) LEAPMED ‘25 13 PHYSIOLOGY - Action Potential and Nerve Physiology ◆ Synaptic Cleft: Extracellular space ◆ Postsynaptic Membrane between the plasma membranes of Components: presynaptic and postsynaptic neurons Ligand-Gated Ion Channels ◆ Unidirectional - one-way transmission (Ionotropic Receptors): from presynaptic to postsynaptic - Open when ◆ Slower but more versatile neurotransmitter communication compared to electrical molecules (ligands) synapses attach to the receptors Electrical signal modification: - Opening allows the enables modulation through entry of ions and excitatory or inhibitory transmission of neurotransmitters electrical signals ◆ Synapses can be found between presynaptic axons and postsynaptic cell C07.3. PRESYNAPTIC VESICLE FUSION (B. A. S. B., bodies or dendrites M. Y. H. V) ➔ Synaptic Activation 1. Action Potential Depolarization: - Action potential reaches the axon terminal - Depolarization triggers the opening of calcium channels - This leads to the influx of calcium ions into the terminal 2. Calcium Binding to Synaptic Vesicles: - Calcium ions bind to proteins called synaptotagmins present in synaptic vesicles Figure 07.2 - 2: Chemical Synapse 3. Initiation of Vesicle Fusion: - Calcium binding to ◆ Presynaptic Membrane Components: synaptotagmins triggers the Voltage-Gated Calcium vesicles to fuse with the Channels: presynaptic cell membrane ○ Opens when an action - Fusion involves potential reaches the complex interactions axon terminals with SNARE proteins ○ Depolarizes the (SNAPs) membrane nearby Neurotransmitter within Note: The quantity of neurotransmitter released into the Vesicles: synaptic cleft is directly proportional to the number of ○ Released through calcium ions released during this process. exocytosis upon binding with calcium ions ➔ Neurotransmitter Release (released outside the 1. Vesicle Fusion: membrane) - Vesicles fuse with the Docking Area: membrane, initiating rapid ○ where neurotransmitter neurotransmitter release into the release occurs synaptic cleft LEAPMED ‘25 14 PHYSIOLOGY - Action Potential and Nerve Physiology 2. Neurotransmitter Binding and transporter proteins to Ligand-Gated Channels: be used again - Neurotransmitters bind to receptors, opening ligand-gated C07.4. POSTSYNAPTIC POTENTIALS (B. A. S. B) ion channels in the postsynaptic neuron ➔ Excitatory Postsynaptic Potential (EPSP) 3. Ion Entry into Postsynaptic Neuron: ◆ Graded; occurs when neurotransmitter - Ions enter the postsynaptic excites the postsynaptic membrane neuron, causing an immediate ◆ Change in electrical activity change change in membrane occurs, but there is no visible response permeability ◆ Depolarizing potential; caused by - Effects can exhibit or inhibit ligand-gated Na+ channels opening the neuron based on the Localized depolarizing signals characteristics of the receptor can lead to long-distance action potentials in postsynaptic ➔ Postsynaptic Potential Creation dendrites ◆ Neurotransmitters binding to ◆ Excitatory neurotransmitters: ligand-gated ion channels create Glutamate postsynaptic potentials (graded Aspartate potentials) Postsynaptic potentials are ➔ Inhibitory Postsynaptic Potential (IPSP) temporary changes in the ◆ Occurs when neurotransmitter inhibits electric polarization of the the postsynaptic membrane membrane ◆ Hyperpolarizing potential; Caused by can either exhibit or inhibit the ligand-gated K+ or Cl- channels opening generation of APs Localized hyperpolarizing signals prevent the generation ➔ Synaptic Deactivation of long-distance action ◆ Neurotransmitters influence electrical potentials in postsynaptic state for a short time only dendrites ◆ Neurotransmitters are deactivated ◆ Inhibitory neurotransmitters: through: Glycine 1. Diffusion Gamma-aminobutyric acid - Some neurotransmitters (GABA) diffuse away (out of reach) from receptors Note: Neurons usually release a single neurotransmitter. and disintegrate Involving multiple neurotransmitters in one neuron adds 2. Enzymatic Degradation complexity to the communication pathways. - Example: Enzymes like acetylcholinesterase C07.5. SUMMATION (L.Y. E.C) break down ➔ To generate an AP, the threshold (-55mV) must be reached. The threshold is achieved through neurotransmitters like summation of multiple EPSP graded potentials. acetylcholine (acetate ➔ Cancellation of potential happens when an and choline) EPSP and IPSP occurs simultaneously. 3. Recycling - Some neurotransmitters are transported back into the presynaptic neuron through LEAPMED ‘25 15 PHYSIOLOGY - Action Potential and Nerve Physiology 2. The frequent EPSP spread from one synapse to the axon hillock Memory Temporal - “Tempo” associated w/ music = device High tempo = “1 song, frequent beats” (Sums up the stimuli from a single presynaptic neuron but moves faster through time - Temporal - Time) C08. NERVE CONDUCTION VELOCITY (M. Y. H. V., B. A. S. B) (F. M. L. P) C08.1. MYELIN SHEATH OF AXONS (M. Y. H. V) Figure 07.5 - 1: Spatial summation in a neuron ➔ Myelin Sheath ➔ Spatial Summation ◆ Acts as an electrical insulator; 1. Several presynaptic neurons decreases ion flow through the simultaneously stimulate neuron, membrane resulting in release of excitatory ◆ Produced by neurotransmitters Oligodendrocytes (CNS) 2. EPSPs spread from several synapses Schwann cells (PNS) (from dendrites to axon hillock) and ◆ Composed of the lipid substance, summate sphingomyelin Memory Spatial ➔ Nodes of Ranvier device Several presynaptic neurons ◆ Gaps in the axon between without (More) Space between each graded potential myelin sheath ◆ Has a high concentration of (Sums up the stimuli from multiple presynaptic neurons voltage-gated Na+ channels (fast Spatial - Space) sodium channels) ◆ Facilitates the rapid conduction of nerve impulses C08.2. SALTATORY CONDUCTION (B. A. S. B) ➔ Saltatory Conduction ◆ Action potentials "jump" between nodes of Ranvier ◆ Increases nerve conduction speed ◆ Electrical current flows through: Extracellular fluid outside the myelin sheath Axoplasm inside the axon Figure 07.5 - 2: Temporal summation in a neuron ➔ Temporal Summation 1. One presynaptic neuron stimulates at high frequency, resulting in release of excitatory neurotransmitters LEAPMED ‘25 16 PHYSIOLOGY - Action Potential and Nerve Physiology charges) or Chemical (difference in concentrations) ◆ Equilibrium Potential is the peak potential where diffusion rate stops; the electrical potential required to balance the chemical potential in the opposite direction. ◆ Resting Membrane Potential - electrical potential difference across the cell membrane’s resting state; inside of the cell is generally more negative ◆ The Nernst Equation is used for Figure 08.2 - 1: Saltatory Conduction computing the net equilibrium potential along the membrane with regard to one C09. CHAPTER SUMMARY (J.B.L.F.T.) (J.G.A.C., specific ion whereas the J.G.C.L.) Goldman-Hodgkin-Katz Equation ➔ Neuronal and Synaptic Physiology takes into account all present ions ◆ Neurons communicate by sending and receiving electrical signals. ➔ Membrane Potential States ◆ Dendrites receive signals from ◆ A cell is under a Polarized state at neighboring neurons while Axons send resting state due to its more negative signals to neighboring neurons. intracellular space. ◆ The Axon Hillock (Initial Segment) ◆ Major Contributors: connects the soma to the axon and is 1. Ion Concentration Gradient the triggering zone for the action 2. Ion Membrane Permeability potential. 3. Polarity/Valence ◆ The Axon Terminal is the end part of 4. Sodium-Potassium ATPase the axon and is responsible for releasing Pump neurotransmitters to relay messages to neighboring neurons ➔ Phases of Change in Membrane Potential ◆ A Synapse is a junction between two 1. Depolarization - From RMP, the neurons - the Presynaptic Neuron membrane becomes less negative and which sends signals toward the synapse is nearing neutral. and the Postsynaptic Neuron which 2. Repolarization - From overshoot or sends signals away from the synapse. depolarization, the membrane becomes ◆ Signal sent by the presynaptic neuron to more negative and is nearing a resting the postsynaptic neuron can be state. Excitatory (neurotransmitters: 3. Hyperpolarization - The state at which aspartate, glutamate, etc.) or the membrane exceeds the negativity of Inhibitory (neurotransmitters: that resting membrane and is commonly glycine, GABA, etc.) referred to as “Afterhyperpolarization ◆ Synapses can either be the faster but or AHP / Undershoot Phase”. less versatile electrical Connexons or the slower but more versatile chemical Synaptic Cleft ➔ Potentials ◆ The driving force behind the movement of ions can be Electrical (attraction of LEAPMED ‘25 17 PHYSIOLOGY - Action Potential and Nerve Physiology Table 09 - 1: Summary of Voltage-Gated Na+ and Ka+ the RMP) → higher chance of nerve Channels Across the Membrane Potential Phases excitability and vice versa. ◆ Resting Membrane Potential Negativity - Inverse relation; more negative RMP (farther from Threshold Potential) → lower chance of nerve excitability and vice versa. ➔ Synaptic Transmission ◆ Presynaptic Membrane Components: Voltage-gated Calcium Channels | Neurotransmitter within vesicles | Docking Area ◆ Postsynaptic Membrane ➔ Graded and Action Potential Components: Ligand-gated Ion Table 09 - 2: Summary of Graded and Action Potential Channels (Ionotropic Receptors) ◆ Presynaptic Vesicle Fusion: Synaptic Activation → Neurotransmitter Release → Postsynaptic Potential Creation (graded potentials) → Synaptic Deactivation ◆ Excitatory Postsynaptic Potential (EPSP) - neurotransmitter excites the postsynaptic membrane. depolarizing potential; caused by ligand-gated Na+ channels opening. ◆ Inhibitory Postsynaptic Potential (IPSP) - neurotransmitter inhibits the postsynaptic membrane. hyperpolarizing ➔ Refractory Period potential; caused by ligand-gated K+ or ◆ Allows the membrane to return to its Cl- channels opening. resting state and ensures unidirectional Table 09 - 3: Summary of Postsynaptic Potentials impulse flow and limited frequency of AP. ◆ Absolute Refractory Period occurs from firing of AP up to the first ⅔ of the repolarization stage wherein a stimulus cannot trigger a subsequent AP. ◆ Relative Refractory Period occurs from the latter ⅓ of the repolarization stage up to the afterhyperpolarization stage Note: wherein an above-threshold stimulus Postsynaptic potentials are graded in nature. can trigger a subsequent AP. Neurons usually release a single neurotransmitter. Involving multiple neurotransmitters in one neuron ➔ Basis of Nerve Excitability adds complexity to the communication pathways. ◆ Threshold Potential Negativity - Direct relation; more negative TP (nearer to LEAPMED ‘25 18 PHYSIOLOGY - Action Potential and Nerve Physiology ◆ Generation of AP is achieved by meeting the -55mV threshold value through the Summation of multiple EPSPs. ◆ Simultaneous occurrence of an EPSP and IPSP leads to cancellation of potential. ◆ Spatial Summation - Sums up the stimuli from multiple presynaptic neurons in a Space ◆ Temporal Summation - Sums up the stimuli from a single presynaptic neuron with a fast Tempo ➔ Saltatory Conduction ◆ AP jumps between Nodes of Ranvier, which gives higher nerve conduction speeds in return ◆ Electrical current flows through: Extracellular fluid - outside the myelin sheath. Axoplasm - inside the axon. REFERENCES BioNinja. (n.d.). Action Potential. https://ib.bioninja.com.au/standard-level/topic-6-huma n-physiology/65-neurons-and-synapses/action-potenti al.html Chapters 5 and 46 of Guyton and Hall Textbook of Medical Physiology, 14th Edition Onsite lecture conducted by Dr. Elaine Cunanan PhysiologyWeb. (2012). Neuronal Action Potential - Graded Potentials versus Action Potentials. https://www.physiologyweb.com/lecture_notes/neuron al_action_potential/neuronal_action_potential_graded _potentials_versus_action_potentials.html PowerPoint presentation on Action Potential and Nerve Physiology FREEDOM WALL How did studying this pile of chronicle feel like? grammar-nazi within? Regardless, 🔗 Confusing? Info-overload? Triggered the 🫡 Here is the link for us to know what you think about the trans LEAPMED ‘25 19