Nerve Potentials

Introduction

• Nerve potentials describe how neurons respond to stimuli and generate electrical signals. Concepts such as threshold, excitability, refractory periods, and ionic movements explain impulse formation, while myelination enhances conduction speed through efficient, saltatory transmission along nerve fibers.

Electrophysiological Aspects

• Transmission of nerve impulses requires generation and propagation of action potentials along the neuronal membrane.
• These processes depend on the activity of specialized ion channels present in the membrane.

Neuronal Ion Channels

• Neuronal membranes contain channels for sodium, potassium, calcium, and chloride ions.
• These channels are classified into leaky channels, gated channels, and energy-dependent pumps.
• Leaky channels allow passive movement of ions and help maintain resting membrane potential.
• Voltage-gated sodium channels are concentrated at nodes of Ranvier and are essential for rapid depolarization.
• Voltage-gated potassium channels help in repolarization of the membrane.
• Voltage-gated calcium channels are mainly present at axon terminals and regulate neurotransmitter release.
• Ligand-gated channels are found on dendrites and cell body.
• They open in response to neurotransmitters and mediate synaptic transmission.
• Mechanically gated channels respond to physical stimuli and generate receptor potentials in sensory endings.
• Adenosine triphosphate–driven pumps, such as the sodium–potassium pump, maintain ionic gradients.
• Proper functioning of these channels is essential for neuronal excitability and communication.

Distribution of Na+ Channels

• Voltage-gated sodium channels are unevenly distributed across neuronal membranes.
• At the cell body, the density is about 50 to 75 channels per square micrometer.
• At the initial segment, density increases to about 350 to 500 channels.
• The myelin-covered regions have very low density, around 25 channels.
• At the nodes of Ranvier, density is highest, about 2000 to 12,000 channels.
• Axon terminals contain 20 to 75 channels per square micrometer.
• In unmyelinated fibers, density is about 110 channels.
• This distribution supports efficient initiation and regeneration of action potentials.

Recording of Nerve Responses

• Nerve activity is studied using intracellular and extracellular recording techniques.
• Electrical stimuli are commonly used because they allow precise control and measurement.

Intracellular Recording

• In intracellular recording, a microelectrode is inserted inside a single nerve fiber.
• A reference electrode is placed on the outer surface of the axon.
• This method records the true membrane potential of the neuron.
• At rest, a negative potential of about −70 millivolts is observed.
• On stimulation, a monophasic action potential is recorded.
• Large diameter axons are preferred as they facilitate electrode insertion.
• This technique provides detailed information about ionic changes across the membrane.

Extracellular Recording

• In extracellular recording, both electrodes are placed outside the nerve fiber.
• At rest, no potential difference is detected because both electrodes are in the same environment.
• Upon stimulation, a biphasic waveform is recorded due to changing extracellular potentials.
• This method is less invasive and is commonly used in clinical studies. It helps assess overall nerve function rather than intracellular events.
• Together, these techniques are essential for understanding nerve excitability and conduction.

Terms Used for Membrane Potentials

• A membrane is said to be polarized when there is a voltage difference between its inner and outer surfaces.
• This resting state is maintained by unequal distribution of ions across the membrane.
• Depolarization occurs when the membrane potential becomes less negative. It usually results from entry of positive ions or exit of negative ions.
• If sufficient, depolarization leads to generation of an action potential.
• Repolarization is the process by which the membrane potential returns toward its resting level. It typically follows depolarization and restores ionic balance.
• Hyperpolarization occurs when the membrane potential becomes more negative than the resting value. This results from increased efflux of positive ions or influx of negative ions.
• These changes in membrane potential are essential for neuronal excitability and impulse conduction.

Genesis Of Nerve Potentials

• Excitability is the ability of a neuron to generate electrical responses when stimulated.
• Neurons respond to electrical, chemical, or mechanical stimuli by altering membrane ion permeability.
• Stimulation causes movement of ions across the membrane, producing a change in membrane potential.
• Weak stimuli produce small, localized voltage changes that decline with distance.
• Stronger stimuli produce larger ionic shifts and can initiate a propagated response.
• Restoration of ionic balance occurs through diffusion of ions and activity of the sodium–potassium pump.
• These mechanisms help return the membrane to its resting state after activation.
• Electrical changes in the membrane appear as wave-like signals when recorded.
• If the stimulus reaches threshold, the response is regenerated and travels along the axon.
• This propagation depends on activation of voltage-gated ion channels along the membrane.
• Information processing occurs mainly in the cell body and dendrites.
• Signal transmission occurs through the axon as electrical impulses.

Types of Nerve Potentials

• Graded potentials are small, local changes in membrane potential.
• They decrease in strength with distance and do not propagate far.
• Action potentials are large, rapid, and self-propagating signals.
• They travel along the entire length of the axon without loss of amplitude.
• Local responses are brief, non-propagated changes that occur at the site of stimulation.
• These mechanisms together ensure efficient signal generation and transmission in neurons.

Electrotonic or Graded Potentials

Definition

• Electrotonic potentials are small, local changes in membrane potential.
• They are non-propagated and occur in response to weak depolarizing or hyperpolarizing stimuli.

Types

• Electrotonic potentials are of two types: catelectrotonic and anelectrotonic.
• Catelectrotonic potential is a depolarizing response produced at the cathodal region during stimulation. It makes the membrane potential less negative and increases excitability.
• Anelectrotonic potential is a hyperpolarizing response produced at the anodal region. It makes the membrane potential more negative and reduces excitability.

Concept

• At rest, the inner surface of the membrane is negative and the outer surface is positive.
• A weak cathodal stimulus allows entry of sodium ions through leaky channels.
• This causes local depolarization and a small change in membrane potential.
• Increasing stimulus strength results in a greater influx of positive ions and a larger voltage change.
• These changes are local and do not propagate along the membrane.
• Repolarization occurs due to outward movement of potassium ions and inward movement of chloride ions.
• Diffusion of sodium away from the stimulated area also helps restore balance.
• The sodium–potassium pump actively restores ionic gradients.
• Electrotonic potentials are mainly recorded in dendrites and cell body.
• They play a key role in integrating incoming signals before action potential generation.

Properties of Graded Potential

Graded nature:

• The amplitude of the response varies with stimulus strength.
• Stronger stimuli produce larger changes in membrane potential.
• The response is proportional and not all-or-none.

Decremental conduction:

• Graded potentials decrease in amplitude with distance from the stimulus site.
• The signal is strongest near the origin and weakens progressively.
• These potentials usually dissipate within a few millimeters.
• The amplitude also declines with time after stimulus application.

Depolarizing or hyperpolarizing responses:

• Graded potentials may be either depolarizing or hyperpolarizing.
• Depolarization occurs due to entry of positive ions into the cell.
• Hyperpolarization occurs due to entry of negative ions or exit of positive ions.
• The direction and shape of the response depend on the type of stimulus applied.

Summation:

• Multiple stimuli can combine to produce a larger response.
• If a second stimulus is applied before the first response ends, their effects add together.
• This can increase both the amplitude and duration of the potential.
• Summation may occur with both depolarizing and hyperpolarizing potentials.

• Graded potentials are essential for integration of signals in dendrites and the cell body.

Forms of Graded Potentials

• Graded potentials occur in different tissues depending on location and function.
• End-plate potential is recorded at the neuromuscular junction of skeletal muscle.
• Receptor potential arises in sensory nerve endings in response to stimuli.
• Synaptic potential occurs in postsynaptic neurons during neurotransmission.
• Pacemaker potential is seen in specialized cells of the heart and smooth muscle, where it initiates rhythmic activity.

Local Response

• Local response is an enhanced graded potential produced by a weak depolarizing stimulus. It occurs when membrane potential decreases by about 7 millivolts from resting level.
• The response is larger than expected for the given stimulus strength.
• Like graded potentials, it shows decremental conduction and fades with distance. It is produced only by depolarizing stimuli, not by hyperpolarizing stimuli.

Ionic Basis of Local Response

• Gradual stimulus increases sodium entry through leaky sodium channels.
• Membrane potential changes from about −70 to −63 millivolts.
• At this level, some voltage-gated sodium channels begin to open.
• Additional sodium influx amplifies depolarization, producing the local response.
• This occurs between approximately −63 and −55 millivolts, approaching threshold.

Types of Stimuli

Threshold, Subthreshold and Suprathreshold Stimuli

• The threshold level is the membrane potential at which an action potential is initiated, usually around −55 millivolts.
• A threshold stimulus is the minimum strength required to reach this level and trigger an action potential.
• This point is also called the firing level of the neuron.
• Subthreshold stimuli are weaker stimuli that fail to reach the threshold.
• They produce only local or graded responses and do not generate action potentials.
• Suprathreshold stimuli are stronger than threshold.
• They successfully trigger action potentials and may increase firing frequency with higher strength.

Strength-Duration Relationship

• The effectiveness of a stimulus depends on both its strength and duration.
• These two factors are inversely related, forming the strength–duration curve.
• Rheobase is the minimum current strength required to excite a tissue.
• A stimulus weaker than rheobase cannot produce a response.
• Utilization time is the minimum duration for which rheobase must be applied to produce excitation.
• Stronger stimuli require shorter durations to elicit a response.
• Chronaxie is the time required for a stimulus of twice the rheobase strength to trigger an action potential. It is an important indicator of tissue excitability.
• Lower chronaxie indicates higher excitability.
• Nerve fibers generally have shorter chronaxie than muscle fibers.

Accommodation

• Accommodation is the failure to generate an action potential when stimulus intensity increases slowly to threshold.
• The neuron adapts to the gradually rising stimulus and does not fire.
• During slow depolarization, some voltage-gated sodium channels open near −63 millivolts.
• These channels quickly become inactivated before enough channels can open simultaneously.
• Therefore, the required number of active sodium channels is not achieved.
• Even if the membrane reaches or exceeds threshold, an action potential may not occur.
• Simultaneously, potassium channels open and allow outward movement of positive ions.
• This counteracts depolarization and prevents excitation. Thus, accommodation reduces neuronal responsiveness to slowly increasing stimuli.

Action Potential

Definition

• Action potential is a rapid, transient change in membrane potential of about 100 millivolts. It is conducted along the axon in an all-or-none manner. It is also called a nerve impulse or spike potential. It begins with gradual depolarization to threshold followed by rapid changes.
• The waveform is regenerated along the axon without loss of amplitude.

Duration and Amplitude

• The duration of a nerve action potential is about 1 millisecond.
• Membrane potential rises from about −70 millivolts to +35 millivolts. It then returns to resting level after completion of the event.

Latent Period

• A latent period exists between stimulus application and onset of action potential. Its duration depends on fiber type, diameter, and electrode distance.
• Action potentials do not summate due to the presence of a refractory period.

Phases of an Action Potential

• Depolarization phase:

1. The membrane potential rises rapidly due to sodium ion influx.
2. It includes slow approach to threshold, rapid upstroke, and overshoot beyond zero.
3. The peak reaches approximately +35 millivolts.

• Repolarization phase:

1. The membrane potential returns toward resting level due to potassium ion efflux.
2. It includes a rapid fall followed by a slower terminal phase.

• Afterhyperpolarization:

1. The membrane becomes temporarily more negative than resting level.
2. It gradually returns to normal resting potential.

• These phases ensure effective generation and propagation of nerve impulses.

Ionic Bases of Action Potential

• The action potential depends on rapid changes in membrane permeability to sodium and potassium ions.
• These changes are mediated by voltage-gated sodium and potassium channels.

Depolarization

• Depolarization begins when a threshold stimulus is reached.
• Initial sodium entry through leaky and a few voltage-gated channels reduces membrane potential from −70 to about −55 millivolts.
• At threshold, many voltage-gated sodium channels open simultaneously.
• This causes a sharp increase in membrane permeability to sodium.
• A rapid influx of sodium ions occurs due to both concentration and electrical gradients.
• Membrane potential rises quickly and becomes positive inside the cell.
• The potential crosses zero and reaches a peak of about +35 millivolts.
• This rapid opening of sodium channels is due to positive feedback, where initial sodium entry triggers further channel activation.
• This process is called auto-activation and produces a steep rising phase.
• During this phase, sodium channel activation gates are open, allowing maximum ion entry.

Membrane Potential Remains Below Na+ Equilibrium Potential

• During depolarization, membrane potential approaches but does not reach the sodium equilibrium potential of about +60 millivolts.
• At the peak, sodium influx stops due to inactivation of sodium channels.
• These channels open briefly and then close rapidly, a process called autodeactivation.
• At the same time, voltage-gated potassium channels are fully open.
• Potassium ions move out of the cell, opposing further depolarization.
• After the membrane potential crosses zero, the inside becomes positive.
• This creates an electrical gradient that resists further sodium entry. Thus, sodium influx declines while potassium efflux increases.
• As a result, the membrane potential stabilizes around +35 millivolts instead of reaching +60 millivolts.
• Although many sodium ions enter the cell, repolarizing forces limit the peak value.

Repolarization

• Repolarization occurs due to opening of voltage-gated potassium channels.
• These channels open more slowly than sodium channels but remain open longer.
• At the peak of the action potential, sodium channels become inactivated.
• Simultaneously, potassium permeability increases markedly.
• Potassium ions move out due to both concentration and electrical gradients.
• This outward movement restores the membrane potential toward resting level.
• The rapid fall in potential results from decreased sodium entry and increased potassium exit.
• Activation of potassium channels represents a negative feedback mechanism.
• As the membrane becomes negative again, potassium efflux slows.
• This produces a slower phase of repolarization, sometimes called after-depolarization.
• Eventually, the membrane returns to resting potential with the help of diffusion and the sodium–potassium pump.
• These processes ensure accurate termination and resetting of the action potential cycle.

Voltage-gated Na+ and K+ Channels

• Voltage-gated sodium channels have two gates: an activation gate and an inactivation gate.
• At rest, the activation gate is closed and the inactivation gate is open. This prevents sodium entry in the resting state.
• Potassium channels have a single gate that remains closed at rest.
• During depolarization, the activation gate of sodium channels opens rapidly.
• Both gates become open briefly, allowing rapid sodium influx. This produces the rising phase of the action potential.
• Potassium channels also begin to open during depolarization. However, they open more slowly compared to sodium channels.
• At the peak of the action potential, the sodium channel inactivation gate closes. This stops sodium entry and initiates repolarization.
• At the same time, potassium channels are fully open.
• This allows potassium efflux, leading to rapid repolarization.
• During late repolarization, sodium channels return to a closed state.
• The activation gate closes, and the inactivation gate gradually reopens.
• Potassium channels begin to close slowly, prolonging the repolarization phase.
• Finally, both sodium and potassium channels return to their resting configuration.
• This coordinated gating ensures proper initiation, propagation, and termination of the action potential.

After-Hyperpolarization

• After-hyperpolarization is a phase where the membrane potential becomes more negative than the resting level. It occurs because some potassium channels remain open after repolarization.
• Continued potassium efflux causes a slow and prolonged undershoot.
• Gradual closure of potassium channels restores the membrane potential to normal resting level.

Ionic Conductance during Action Potential

• Ionic conductance refers to the ease with which ions pass through the neuronal membrane. It reflects membrane permeability and is inversely related to electrical resistance.

Sodium Conductance

• Sodium conductance increases gradually as the membrane approaches threshold. It then rises sharply during depolarization due to opening of voltage-gated sodium channels.
• Conductance reaches a peak at the height of the action potential.
• After the peak, it declines rapidly as sodium channels become inactivated.

Potassium Conductance

• Potassium conductance increases after the rise in sodium conductance.
• Initially, it rises slowly during early depolarization. It reaches its maximum during the repolarization phase.
• This increase is due to opening of voltage-gated potassium channels.
• Potassium conductance declines slowly and remains elevated during after-hyperpolarization.

Ionic Activity after Action Potential

• After an action potential, there is a slight increase in intracellular sodium and decrease in potassium.
• This imbalance is corrected by the sodium–potassium pump, which restores ionic gradients.
• Only a small fraction of total ions participates in a single action potential. Therefore, the overall intracellular ionic concentration changes minimally. However, repeated action potentials without correction would disrupt ionic gradients.
• This would impair further generation of action potentials.
• Continuous activity of ion pumps ensures maintenance of neuronal excitability and function.

Effects of Extracellular Ionic Changes

• Changes in extracellular ion concentration significantly influence membrane potential and excitability.
• A decrease in extracellular sodium reduces the amplitude of action potentials.
• This occurs because the inward sodium gradient becomes weaker.
• An increase in extracellular sodium may slightly increase action potential amplitude.
• A decrease in extracellular potassium makes the membrane potential more negative.
• This hyperpolarization reduces neuronal excitability.
• An increase in extracellular potassium brings the membrane potential closer to threshold.
• This enhances neuronal excitability and may lead to spontaneous activity.
• A decrease in extracellular calcium reduces membrane stability.
• The resting potential moves closer to threshold, increasing excitability.
• This can produce clinical manifestations such as tetany.
• An increase in extracellular calcium stabilizes the membrane.
• The resting potential moves further from threshold, reducing excitability. Thus, proper regulation of extracellular ions is essential for maintaining normal nerve function and stability.

Ion Channel Blockers

Na+ Channel Blockers

• Drugs such as lidocaine and procaine block voltage-gated sodium channels.
• This prevents generation and propagation of action potentials.
• Neurotoxins like tetrodotoxin and saxitoxin also inhibit sodium channels.
• These toxins can cause severe paralysis and may be fatal.

Local Anesthetics

• Local anesthetics diffuse through the membrane and block sodium channels from inside.
• This reduces transmission of pain and sensory signals.
• Smaller diameter nerve fibers are more sensitive than larger fibers.

Membrane Toxins

• Tetrodotoxin is found in puffer fish, while saxitoxin is present in shellfish.
• These toxins prevent sodium entry, leading to loss of nerve conduction.
• Some organisms possess resistant sodium channels to survive these toxins.

K + Channel Blockers

• Agents such as tetraethylammonium and 4-aminopyridine block potassium channels. This delays repolarization and prolongs the action potential.
• They are mainly used in electrophysiological research.

Na+– K+ ATPase Blocker

• Drugs like digitalis inhibit the sodium–potassium pump.
• This alters ionic gradients and affects cellular excitability.

All-or-None Law

Definition

• The all-or-none law states that an action potential occurs with a constant amplitude and shape.
• A subthreshold stimulus does not produce an action potential.
• A threshold stimulus is required to initiate excitation.
• Suprathreshold stimuli also produce action potentials of identical amplitude and duration.
• This uniformity is maintained when physiological conditions remain constant.

Mechanism

• When depolarization reaches about 15 millivolts, voltage-gated sodium channels open rapidly. This triggers a large and automatic influx of sodium ions.
• Once threshold is reached, further increase in stimulus strength does not enhance the response.
• The number of available sodium channels in the membrane is relatively constant. Therefore, sodium entry becomes independent of stimulus intensity after threshold.
• If sufficient depolarization occurs, a full action potential is generated.
• If threshold is not reached, no action potential occurs. Thus, the response is either complete or absent, with no intermediate forms.
• This principle ensures reliable signal transmission along nerve fibers.

Refractory Periods

• The refractory period is the time during which a neuron shows reduced or no response to a second stimulus.
• During the absolute refractory period, no stimulus can produce another action potential.
• During the relative refractory period, a stronger-than-normal stimulus is required to elicit a response.
• These periods ensure proper timing and prevent continuous excitation.

Absolute Refractory Period

Definition and Duration

• The absolute refractory period is the phase during which no second action potential can be generated.
• This occurs regardless of the strength or duration of the stimulus. It extends from the onset of depolarization to about one-third of repolarization.

Mechanism

• During this period, voltage-gated sodium channels are in the inactivated state.
• The inactivation gates remain closed and prevent sodium entry.
• These channels cannot reopen until they return to the resting state. Therefore, even a strong stimulus fails to produce another action potential.

Physiological Importance

• The absolute refractory period limits the maximum firing frequency of neurons. It determines how rapidly action potentials can be generated.
• Large diameter fibers have a shorter refractory period and higher firing rates.
• Small diameter fibers have a longer refractory period and lower firing rates. It ensures unidirectional conduction of impulses along the axon.
• This prevents backward propagation of action potentials.
• Overall, it maintains proper timing and coordination of neuronal signaling.

Relative Refractory Period

Definition and Duration

• The relative refractory period follows the absolute refractory period.
• During this phase, a second action potential can be generated only by a suprathreshold stimulus. It extends from the end of absolute refractoriness to the beginning of after-depolarization.

Mechanism

• Not all voltage-gated sodium channels recover simultaneously.
• Some channels return to the resting state and become available for activation.
• These recovered channels can open in response to a strong stimulus.
• At the same time, many potassium channels remain open.
• This maintains a more negative membrane potential and opposes depolarization.
• A stronger stimulus is required to overcome this reduced excitability. It activates additional sodium channels across a wider membrane area.
• This allows sufficient sodium influx to generate another action potential.

Physiological Significance

• Membrane excitability varies during the action potential cycle.
• Excitability increases as the membrane potential approaches threshold. It decreases when the membrane is more negative than resting level.
• The relative refractory period ensures controlled frequency of nerve impulses. It prevents excessive and continuous neuronal firing.

Initiation and Propagation of Action Potential

Initiation of Action Potential

• Action potentials are generated mainly in the axon, not in dendrites or cell body.
• The first impulse arises at specialized regions called trigger zones.
• In sensory neurons, initiation occurs at the first node of Ranvier.
• In motor neurons, it begins at the axon hillock and initial segment.
• These regions have a high density of voltage-gated sodium and potassium channels.
• Synaptic inputs from dendrites and cell body are integrated at the soma.
• If the membrane potential reaches threshold at the axon hillock, an action potential is initiated.

Propagation of Action Potential

• Once generated, the action potential is transmitted along the axon by regeneration at successive segments.
• This ensures that the signal travels without loss of amplitude.

• In myelinated fibers, conduction occurs by saltatory transmission.
• The impulse jumps from one node of Ranvier to the next, increasing speed.
• In unmyelinated fibers, conduction is continuous and slower.

Factors Affecting Conduction Velocity

• Myelination increases conduction speed by reducing ion leakage and enabling efficient signal transmission.
• Greater degree of myelination leads to faster conduction.
• Axon diameter also influences conduction velocity.
• Larger diameter fibers conduct impulses faster due to lower internal resistance.
• These factors ensure efficient and rapid nerve impulse transmission throughout the nervous system.

In Unmyelinated Axon

• In an unmyelinated axon, conduction occurs by continuous propagation along the membrane.
• At the site of action potential, there is a large influx of positive ions, forming a current sink.
• These positive charges spread to adjacent resting regions of the membrane.
• The neighboring membrane has a resting potential of about −70 millivolts.
• Local current flow reduces this potential toward threshold.
• When threshold is reached, voltage-gated sodium channels open.
• This generates a new action potential in the adjacent segment.
• The process repeats sequentially along the axon.
• Each segment undergoes depolarization followed by repolarization. This results in step-by-step propagation of the impulse.
• The action potential does not physically travel.
• Instead, it triggers generation of a new action potential ahead.
• Uniform distribution of ion channels ensures identical amplitude throughout conduction.
• During propagation, there is coordinated opening of sodium channels and delayed opening of potassium channels. This maintains the characteristic waveform of the action potential.
• Local current circuits are established around the active region.
• Inside the membrane, positive charges move forward from the active site.
• Outside the membrane, positive charges flow toward the active region. This creates a circular current flow that helps restore resting conditions behind the impulse.
• Continuous conduction in unmyelinated fibers is slower compared to myelinated fibers. However, it ensures effective transmission in small diameter nerve fibers. Thus, propagation occurs by sequential depolarization and regeneration along the entire membrane.

In Myelinated Axon (Saltatory Conduction)

• In myelinated axons, ion channels are concentrated mainly at the nodes of Ranvier.
• The myelin sheath acts as an electrical insulator, reducing ion movement across the membrane.
• Due to insulation, there is minimal ion leakage in myelinated segments.
• Positive charges spread rapidly along the axon as local currents. This allows the depolarizing current to travel a longer distance without significant decay.
• The local current moves passively and decreases gradually with distance. However, the internodal distance is short enough for the current to reach the next node.
• At the node of Ranvier, a high density of voltage-gated sodium channels is present.
• When the depolarizing current reaches threshold, a new action potential is generated. Thus, action potentials are produced only at the nodes, not along the entire membrane.
• The impulse appears to “jump” from one node to the next.
• This mode of conduction is called saltatory conduction. It significantly increases the speed of impulse transmission.
• Saltatory conduction also reduces energy expenditure by limiting ion exchange to nodal regions.
• Overall, myelination ensures rapid, efficient, and reliable nerve impulse propagation.

Advantages in Myelinated Axon

• Myelination significantly increases the velocity of nerve impulse conduction.
• Conduction occurs by saltatory transmission, allowing rapid signal propagation.
• Ionic exchange occurs only at the nodes of Ranvier, not along the entire membrane. This reduces the total membrane area involved in ion movement.
• As a result, fewer ions need to be transported back by the sodium–potassium pump. This leads to lower energy expenditure compared to unmyelinated fibers.
• In contrast, unmyelinated axons require continuous activation of ion channels along their length.
• This increases metabolic demand and slows conduction.

Direction of Propagation of Action Potential

• In motor neurons, impulses travel from the axon hillock to the axon terminal.
• In sensory neurons, impulses move from peripheral regions toward the central nervous system.
• This forward movement is called anterograde conduction.
• The axon contains many voltage-gated sodium channels that facilitate rapid propagation.
• Backward conduction does not normally occur due to the refractory state of the membrane.
• After depolarization, sodium channels remain inactivated temporarily. This prevents re-excitation of the previously activated segment. Therefore, the impulse travels only in one direction under normal conditions. However, if stimulation occurs in the middle of the axon, impulses may spread in both directions.

Table 23.1: Differences between graded potential and action potential.

Feature	Graded Potential	Action Potential
Amplitude	Varies with stimulus strength; usually small	Fixed amplitude once threshold is reached; relatively large
Conduction	Decreases with distance (decremental)	Propagates without loss (all-or-none)
Summation	Can undergo temporal and spatial summation	Cannot be summated
Nature	May be depolarizing or hyperpolarizing	Always a rapid depolarizing event
Mechanism	Involves ligand-gated or leak channels	Involves voltage-gated ion channels
Threshold	No fixed threshold required	Requires a definite threshold potential
Refractory Period	Absent	Present (absolute and relative phases)