Type of signal | Depolarizing (e.g., Na^+$) or hyperpolarizing (e.g., Cl^-)</p></td><tdcolspan="1"rowspan="1"style="text−align:left;"><p>Depolarizing</p></td></tr><tr><tdcolspan="1"rowspan="1"style="text−align:left;"><p><strong>Strengthofsignal</strong></p></td><tdcolspan="1"rowspan="1"style="text−align:left;"><p>Dependsoninitialstimulus;canbesummed</p></td><tdcolspan="1"rowspan="1"style="text−align:left;"><p>Isalwaysthesame("all−or−none");cannotbesummed</p></td></tr><tr><tdcolspan="1"rowspan="1"style="text−align:left;"><p><strong>Whatinitiatesthesignal</strong></p></td><tdcolspan="1"rowspan="1"style="text−align:left;"><p>Entryofionsthroughchannels</p></td><tdcolspan="1"rowspan="1"style="text−align:left;"><p>Above−thresholdgradedpotentialatthetriggerzone</p></td></tr><tr><tdcolspan="1"rowspan="1"style="text−align:left;"><p><strong>Uniquecharacteristics</strong></p></td><tdcolspan="1"rowspan="1"style="text−align:left;"><p>Nominimumlevelrequiredtoinitiate;twosignalscloseintimewillsum</p></td><tdcolspan="1"rowspan="1"style="text−align:left;"><p>Thresholdstimulusrequired;refractoryperiod(nosummation)</p></td></tr></tbody></table><h4id="9d832d4a−0403−46b7−a63b−5cbb64153b2f"data−toc−id="9d832d4a−0403−46b7−a63b−5cbb64153b2f"collapsed="false"seolevelmigrated="true">ActionPotentials(APs)−SummaryThusFar(Page69)</h4><ul><li><p>APsareinitiatedinan"all−or−none"mannerwhenthesummedgradedpotentialatthetriggerzoneexceedsthethresholdvoltage.</p></li><li><p>APsmaintainthesamesize(amplitude)astheytraveloverlongdistancesandareidenticaltooneanother.</p></li><li><p>APsoccurduetoalterationsinthepermeabilityofNa^+$ and K^+$ ions through voltage-gated channels. Readings (Page 70)Nervous System Fundamentals: Section 11.1 - 11.3inChapter11FundamentalsoftheNervousSystemandNervousTissueinMarieb(10^{th}/11^{th}Ed).</p></li><li><p><strong>RestingMembranePotential</strong>:Section3.5:SelectivediffusionestablishesthemembranepotentialinChapter3Cells:TheLivingUnitandSections11.4 - 11.5inChapter11FundamentalsoftheNervousSystemandNervousTissueinMarieb(10^{th}/11^{th}Ed).</p></li><li><p><strong>ActionPotentials</strong>:Section11.6inChapter11FundamentalsoftheNervousSystemandNervousTissueinMarieb(10^{th}/11^{th}Ed).</p></li></ul><h4id="bb1162a2−7ee3−483f−b89b−943539d3ec5b"data−toc−id="bb1162a2−7ee3−483f−b89b−943539d3ec5b"collapsed="false"seolevelmigrated="true">ActionPotentialsPart2(Page71)</h4><h4id="5942b444−2d81−4685−925e−2bb0ce56aa0a"data−toc−id="5942b444−2d81−4685−925e−2bb0ce56aa0a"collapsed="false"seolevelmigrated="true">LearningObjectivesforAP(Page72)</h4><ol><li><p>Drawandlabelthetypicalactionpotential(AP)curveofmVversustime,indicating:RestingMembranePotential(RMP),Subthresholdpotentials,Depolarization,Repolarization,Hyperpolarization,andRefractoryPeriods.</p></li><li><p>Explaintheabovesub−pointsintermsofsodium(Na^+$) and potassium (K^+$) channels. Explain the "all or nothing" principle of AP propagation and the role summation plays in this process. Differentiate between slow and fast nerve transmission and the role of myelin sheaths. Discuss how action potential generation is affected in Multiple Sclerosis and by local anesthetics like Lignocaine. Time Course of the Action Potential (Page 73)The action potential curve illustrates the typical changes in membrane potential (mV) over time (msec), along with corresponding ion permeability changes. Resting State: Membrane potential is at RMP, e.g., -70mV.</p></li><li><p><strong>Threshold</strong>:Astimulusdepolarizesthemembranetothethreshold(e.g.,-55mV).</p></li><li><p><strong>RisingPhase(Depolarization)</strong>:Rapidincreaseinmembranepotential,becomingpositive(e.g.,upto+30mV),primarilyduetoNa^+$ influx. Falling Phase (Repolarization): Rapid decrease in membrane potential, returning towards negative values, primarily due to K^+$ efflux. After-hyperpolarization: A brief period where the membrane potential becomes even more negative than RMP (e.g., -90mV)beforereturningtorest.</p></li></ul><p>Ionpermeabilitychangesconcurrently:Na^+$ permeability rapidly increases during depolarization then drops, while K^+$ permeability increases more slowly during repolarization and decreases during hyperpolarization. Generating an Action Potential: Four Main Steps (Page 74)1. Resting State (Page 74, 76)All gated Na^+$ and K^+$ channels are closed. Only leakage channels for Na^+$ and K^+$ are open, maintaining the resting membrane potential (RMP). Na^+$ channels: Each has two voltage-sensitive gates: Activation gates: Closed at rest, open with depolarization, allowing Na^+$ to enter the cell. Inactivation gates: Open at rest, but block the channel shortly after it opens, preventing more Na^+$ from entering.
K^+$ channels: Each has one voltage-sensitive gate:
Key Players: Voltage-Gated Channels (Page 75, 78)Important Points to Understand (Page 80)Once the Na^+$ channels are opened, Na^+$ floods into the cell along its electrochemical gradient. For a short period after this, the Na^+$ channels are blocked (inactivated), meaning another AP cannot be generated in that specific region. This is critical because it means the only available channels for the AP to move into are those "in front" of it (which are yet to be opened and subsequently closed/inactivated). The consequence of this transient inactivation is that the AP can only propagate in one direction along the axon.
2. Depolarization: Na^+$ Influx (Page 77, 81-83)Depolarizing local currents cause voltage-gated Na^+$ channels to open, and Na^+$ rushes into the cell. Both Na^+$ activation and inactivation gates are initially open. This Na^+$ influx causes further depolarization, which in turn opens more Na^+$ channels (positive feedback loop). As a result, the intracellular fluid (ICF) becomes less negative. When the membrane potential reaches the threshold (between -55mVand-50mV),thispositivefeedbackmechanismcausestherapidopeningof<em>all</em>remainingNa^+$ channels. This leads to a large action potential spike, and the membrane polarity momentarily reverses, jumping to approximately +30 mV. This is the first AP step; depolarization literally means "loss of polarity." Na^+$ gates cannot immediately respond to another AP: The inactivation gate's movement is coupled to the activation gate but is slower. This slight delay (few /10,000′sofasecond)allowssufficientNa^+$ entry before the inactivation gate closes, blocking the channel. So, while both gates are activated simultaneously, the channel opens quickly, permits Na^+$ inflow, and then the inactivation gate closes, temporarily blocking it and preventing immediate re-firing.
3. Repolarization: Na^+$ Channels Inactivate, K^+$ Channels Open (Page 84-86)Repolarization is the second AP step. While Na^+$ influx caused depolarization, the escape of positive charge (via K^+$ efflux) repolarizes the membrane. Na^+$ channel inactivation gates close, causing the membrane permeability to Na^+$ to decline back to its resting state. This halts the rising phase of the AP spike. Concurrently, voltage-gated K^+$ channels, which open slowly in response to depolarization, are now fully open. K^+$ exits the cell down its electrochemical gradient, causing the membrane potential to return towards its resting negative value.
Repolarization & K^+$ Channels (Page 87)Important point: K^+$ channels open slowly compared to Na^+$ channels. By the time K^+$ floods out of the cell along its chemical gradient, most Na^+$ channels have already inactivated and closed. The K^+$ channels also close slowly, often leading to a brief period where the membrane potential approaches the equilibrium potential for K^+$ (EK, approximately −90 mV), resulting in hyperpolarization. This hyperpolarization is corrected over time by slight net Na^+$ inflow (and the Na^+/K^+ATPasepump),re−establishingthenormalRMP,andtheaxonbecomesreadytofireagain.</p></li></ul><h5id="aa0f0a5d−50b9−4e05−8578−8c1cc00ee1f4"data−toc−id="aa0f0a5d−50b9−4e05−8578−8c1cc00ee1f4"collapsed="false"seolevelmigrated="true">4.Hyperpolarization:SomeK^+$ Channels Remain Open, Na^+$ Channels Reset (Page 88-90) Hyperpolarization is the third AP step. Due to the slow closing of K^+$ channels, some remain open, allowing excessive K^+$ efflux. This causes the inside of the membrane to become even more negative than the resting state, leading to a slight dip below the resting voltage. During this phase, the Na^+$ channels also begin to reset from their inactivated state to their closed-at-rest state. Eventually, the slow K^+$ channels close, and the Na^+/K^+ATPasepumpandleakagechannelsrestorethemembranetoitsrestingpotential.</p></li></ul><h4id="82969453−896e−492a−8512−abd8d2008316"data−toc−id="82969453−896e−492a−8512−abd8d2008316"collapsed="false"seolevelmigrated="true">RoleoftheNa^+/K^+ATPasePump(Page91)</h4><ul><li><p>TheNa^+/K^+−ATPasepumpplays<strong>nodirectrole</strong>inthe<em>generation</em>ofindividualactionpotentials.</p></li><li><p>ThereareampleionsavailablefornumerousAPgenerationswithoutimmediatepumpactivity.</p></li><li><p>However,thepumpisessentialforthe<em>long−termmaintenance</em>oftheiongradients(lowintracellularNa^+andhighintracellularK^+$). It actively transports 3 Na^+$ ions out of the cell for every 2K^+$ ions it pumps into the cell, against their respective electrochemical gradients, preventing the ionic concentrations from running down over time.
APs – Some Final Details (Page 92)During an action potential, there is a simultaneous increase in both Na^+$ and K^+$ permeability. However, the increase in Na^+$ permeability is initially far greater and of shorter duration than the K^+$ increase. K^+$ outflow ceases because the repolarization of the membrane switches off the voltage-gated K^+$ channels. In both cases (Na^+$ and K^+$ channels), the changing membrane charge directly influences the function and conformation of the channel proteins involved, causing them to open and close.
Chemicals That Affect Electrical Signals in Neurons (Page 94)Certain chemicals can specifically block ion channels, thereby affecting electrical signaling: Tetrodotoxin (TTX): Blocks voltage-gated Na^+$ channels. Found in puffer fish. Saxitoxin: Blocks voltage-gated Na^+$ channels. Produced by marine organisms causing "red tide." Procaine: Local anesthetic that blocks voltage-gated Na^+$ channels. Tetraethylammonium chloride (TEA): Blocks voltage-gated K^+$ channels. Ethanol: Depresses action potentials and depolarizes the membrane; it can be inhibitory in higher doses and excitatory in low doses, affecting Ca2+ and assorted receptor-operated channels.
Refractory Periods (Page 95 & 97)Refractory periods are critical for regulating the timing and direction of action potential propagation. Absolute Refractory Period: For approximately 1 msec after an AP begins, a second AP cannot be triggered, regardless of how strong the stimulus is. This occurs because voltage-gated Na^+$ channels are either open or in their inactivated state and cannot respond to a new stimulus. Relative Refractory Period: Following the absolute refractory period, during this phase, it is possible to generate a second action potential, but it requires a stronger-than-normal stimulus to reach the threshold levels.
The “All or Nothing” Rule (Page 96)The generation of an action potential is an "all or nothing" event. If a stimulus reaches threshold, a full AP of consistent amplitude (size) is generated. If the stimulus is subthreshold, no AP occurs. The amplitude of an individual AP does not change once initiated. However, the frequency (rate) of a series of action potentials can change, indicating the strength of the initial stimulus (though not indefinitely).
AP Propagation: A Final Series of Slides (Page 98-102)Initiation: A graded potential above threshold reaches the trigger zone of the axon. Depolarization: Voltage-gated Na^+$ channels open, and Na^+$ enters the axon. Local Current Flow: Positive charge flows into adjacent sections of the axon due to local current flow. Sequential Depolarization: Local current flow from the active region causes new sections of the membrane to depolarize to threshold. Unidirectional Conduction: The refractory period in the preceding section prevents backward conduction. Meanwhile, loss of K^+$ from the cytoplasm repolarizes the membrane in the active region.
Conduction Velocity in Axons (Page 103-107)Axons vary significantly in their conduction speed. For example, postural reflexes are fast (up to 100 m/s), whereas control of internal organs is slower, as high speed is less critical for survival in these systems. Fast neurons are also more "expensive" to construct and maintain. Rate of propagation is dependent on two main factors: Axon Diameter: The larger the axon diameter, the lower the internal resistance to ion flow. This allows local currents to spread faster and further, leading to a faster signal transmission, similar to how thicker electrical wiring offers less resistance. Degree of Myelination: Myelin sheaths act as insulation around the axon. In myelinated axons, the signal is forced to "jump" between unmyelinated gaps called Nodes of Ranvier. This type of propagation, known as saltatory conduction, is significantly faster than continuous conduction.
Conduction in Bare Plasma Membranes (Dendrites) (Page 104): In bare plasma membranes (without voltage-gated channels, like dendrites), voltage signals decay over distance because current leaks across the membrane. This is why graded potentials are short-distance signals.
Conduction in Non-Myelinated Axons (Continuous Conduction) (Page 105): In non-myelinated axons, voltage-gated Na^+$ and K^+$ channels regenerate the action potential at each point along the axon. This prevents voltage decay. However, this process is relatively slow because it takes time for ions to move and for the gates of channel proteins to open and close sequentially at every point, which is necessary for voltage regeneration.
Role of Myelin Sheaths (Saltatory Conduction) (Page 106-107): Myelinated axons perform saltatory conduction, where the AP appears to "jump" from one Node of Ranvier to the next. The myelin sheath acts as an insulator, preventing current leakage and allowing the local current to spread rapidly between nodes. APs are generated only at the unmyelinated gaps (myelin sheath gaps or Nodes of Ranvier), where voltage-gated channels are concentrated. Saltatory conduction is approximately 30 times faster than continuous conduction. Clinical Relevance: Sharp, fast pain fibers are typically myelinated, while slower, aching pain fibers are often non-myelinated.
Multiple Sclerosis (Page 108)Multiple Sclerosis (MS) is an autoimmune demyelinating disease where the immune system attacks and damages the myelin sheaths of neurons in the central nervous system. This demyelination causes signal transmission to slow down or even fail, leading to a variety of neurological symptoms. Patients typically suffer from muscle weakness, chronic fatigue, difficulties with walking and coordination, and may eventually experience vision loss.
Local Anaesthetics (Page 109)Cocaine derivatives, such as Lignocaine (Lidocaine), are commonly used as local anesthetics. They work by blocking the opening of voltage-gated Na^+$ channels. By preventing Na^+$ entry into the neurons, these drugs reduce or completely inhibit the propagation of action potentials. This leads to reduced (or no) pain transmission and, in higher concentrations, can cause skeletal muscle paralysis in the affected area. Cold can also be used as a simple method to help anesthetize tissues. Cold slows down all metabolic reactions and nerve conduction velocities, thereby reducing nerve excitability and pain sensation.
Readings (Page 111)Nervous System Fundamentals: Section 11.1−11.3 in Chapter 11 Fundamentals of the Nervous System and Nervous Tissue in Marieb (10th/11th Ed). Resting Membrane Potential: Section 3.5: Selective diffusion establishes the membrane potential in Chapter 3 Cells: The Living Unit and Sections 11.4−11.5 in Chapter 11 Fundamentals of the Nervous System and Nervous Tissue in Marieb (10th/11th Ed). Action Potentials: Section 11.6 in Chapter 11 Fundamentals of the Nervous System and Nervous Tissue in Marieb (10th/11th Ed).
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