Chapter 3 Neurophysiology The Structure and Functions of the Cells of the Nervous System

At resting membrane potential, which direction would K⁺ ions move if K⁺ channels were open, and why?

Out of the cell due to the concentration gradient.

• There is more K⁺ inside the cell than outside.

• The concentration gradient drives K⁺ out of the cell.

• The electrical gradient would want to keep K⁺ in (because the inside is negative), but the concentration gradient is stronger at rest.

What is the Resting Membrane Potential (RMP)?

It’s the baseline electrical charge across the neuron's membrane (~ -70 mV), with the inside more negative than the outside.

What maintains the RMP?

Ion gradients (especially K⁺), leaky K⁺ channels, and the Na⁺/K⁺ pump.

What are Graded Synaptic Potentials (GSPs)?

Small, local changes in membrane potential in response to synaptic input (EPSPs or IPSPs).

What determines if a GSP is excitatory (EPSP) or inhibitory (IPSP)?

The type of ion channel that opens:

• EPSP: Na⁺ or Ca²⁺ in (depolarization)

• IPSP: Cl⁻ in or K⁺ out (hyperpolarization)

What is summation?

GSPs add up at the axon hillock. If the combined input reaches the threshold, an action potential is triggered.

What is the Action Potential (AP)?

A rapid, all-or-nothing electrical signal that travels down the axon once threshold is reached (~ -55 mV).

Sequence of neuronal communication?

1. RMP (stable state)

2. GSP (graded changes due to synaptic input)

3. Summation (inputs integrated at axon hillock)

4. AP (if threshold is reached, full signal fires)

What triggers an Action Potential?

The summation of EPSPs brings the membrane potential above threshold (~ -55 mV), triggering a rapid depolarization.

What happens during the Action Potential?

The membrane potential spikes to about +35 mV due to the opening of voltage-gated Na⁺ channels.

Is the Action Potential graded or all-or-nothing?

All-or-nothing – once threshold is reached, the AP always occurs with the same size and shape

How is the strength of a signal encoded if all APs are the same size?

Frequency coding – stronger stimuli cause more frequent action potentials, not bigger ones.

What follows an Action Potential?

A refractory period, during which it's harder (or impossible) for another AP to occur.

What is the refractory period?

• Absolute Refractory Period: No new AP can be generated (Na⁺ channels are inactivated).

• Relative Refractory Period: A stronger-than-normal stimulus is needed (membrane is hyperpolarized).

What are passive (leak) ion channels and their function?

Always open; they maintain the Resting Membrane Potential (RMP) by allowing ions (especially K⁺) to flow down their electrochemical gradients.

What do ligand-gated ion channels respond to, and what process are they involved in?

Open in response to neurotransmitter binding; generate Graded Synaptic Potentials (EPSPs or IPSPs) at the dendrites and cell body.

What triggers voltage-gated ion channels, and where are they critical?

Open in response to changes in membrane potential; essential for generating and propagating the Action Potential along the axon.

What is the threshold for triggering an action potential?

Approximately -60 mV; if the membrane potential reaches this level at the axon hillock, an AP is initiated.

What happens during the Upswing (Rising Phase) of the action potential?

Voltage-gated Na⁺ channels open, causing a rapid influx of Na⁺ and depolarization of the membrane.

What is the Overshoot phase of an action potential?

The membrane potential becomes positive (peaks around +35 mV) due to continued Na⁺ influx.

What occurs during the Repolarization Phase (Falling Phase)?

Na⁺ channels inactivate and voltage-gated K⁺ channels open, causing K⁺ to exit the cell and the membrane to repolarize.

What does “All-or-None” mean in the context of an action potential?

If the threshold is reached, the neuron will always fire an AP of the same size, regardless of stimulus strength.

What is Afterhyperpolarization (AHP)?

The membrane potential becomes more negative than RMP due to continued K⁺ efflux before returning to rest.

Why is the threshold for activation of an action potential different in various parts of the neuron?

Because the distribution of voltage-gated sodium (Na⁺) channels is not uniform throughout the neuron.

Which part of the neuron typically has the lowest threshold for action potential initiation?

The axon hillock (initial segment), due to the highest density of voltage-gated Na⁺ channels.

Do dendrites and the soma initiate action potentials? Why or why not?

No, they usually do not because they have fewer voltage-gated Na⁺ channels and thus higher thresholds.

Which ion channel is responsible for the upswing (rising phase) of the action potential?

Voltage-gated Na⁺ (sodium) channels.

What causes the repolarization phase (falling phase) of the action potential?

The opening of voltage-gated K⁺ (potassium) channels, leading to K⁺ efflux.

What happens after the action potential that causes the membrane to briefly become more negative than the resting potential?

Hyperpolarization, due to continued K⁺ efflux through open voltage-gated K⁺ channels.

What are the states of the activation and inactivation gates of a voltage-gated Na⁺ channel at rest?

Activation gate is closed, inactivation gate is open.

What happens to both gates of the voltage-gated Na⁺ channel during depolarization?

Both the activation and inactivation gates open, allowing Na⁺ to flow in.

What happens to the Na⁺ channel gates after depolarization progresses?

The inactivation gate closes, activation gate remains open—Na⁺ can no longer enter.

What must happen for the voltage-gated Na⁺ channel to reset and be ready for another action potential?

The neuron must repolarize, so the activation gate closes and inactivation gate reopens.

How many gates does a voltage-gated K⁺ channel have?

Only one activation gate.

What is required for the activation of voltage-gated K⁺ channels?

A longer period of depolarization.

Why are voltage-gated K⁺ channels called Delayed Rectifiers?

Because they open more slowly and only after a higher level of depolarization is reached.

What is the primary function of voltage-gated K⁺ channels in an action potential?

They are responsible for the repolarization phase by allowing K⁺ efflux (K⁺ leaving the cell).

What initiates the action potential?
Back:

• A few Na⁺ voltage-gated channels open due to EPSPs.

• If threshold (~ -55 to -60 mV) is reached at the axon hillock, an action potential is triggered.

What happens during the rising phase (depolarization)?

• Many Na⁺ voltage-gated channels open.

• Na⁺ rushes into the cell, causing a rapid depolarization.

• Membrane potential reaches approximately +35 mV.

What happens at the peak of the action potential?

• Na⁺ channels become inactivated (not simply closed).

• K⁺ voltage-gated channels open, starting repolarization.

What happens during repolarization?

• K⁺ exits the cell through voltage-gated K⁺ channels.

• The membrane potential becomes more negative, returning toward resting levels.

What causes afterhyperpolarization (AHP)?

• K⁺ channels remain open longer, allowing extra K⁺ to leave.

• Membrane becomes more negative than resting potential (hyperpolarized).

How is resting membrane potential restored?

• Voltage-gated K⁺ channels close.

• Na⁺/K⁺ pump and leaky channels reestablish RMP (~ -70 mV).

• Neuron is ready to fire again after the refractory period.

What are the key ion channels involved in an action potential?

• Na⁺ voltage-gated channels: depolarization (rising phase)

• K⁺ voltage-gated channels: repolarization and hyperpolarization

• Leaky channels and Na⁺/K⁺ pump: maintain RMP

What is the Absolute Refractory Period?

A period after an action potential during which a neuron cannot fire again, no matter how strong the stimulus.

What causes the Absolute Refractory Period?

The inactivation of voltage-gated Na+ channels.

What is the Relative Refractory Period?

A period after the Absolute Refractory Period during which a neuron can fire again, but only with a stronger-than-usual stimulus.

What causes the Relative Refractory Period?

The hyperpolarization that occurs after the action potential due to continued K+ efflux.

What is the resting membrane potential of a neuron?

Approximately -70 mV.

What causes initial depolarization in a neuron?

Summation of EPSPs (excitatory postsynaptic potentials).

Which ion channels open to initiate the action potential?

Voltage-gated Na+ channels.

What happens when Na+ channels open during an action potential?

Na+ rushes in, causing depolarization of the neuron membrane.

What is the threshold for firing an action potential?

Around -60 mV, reached at the axon hillock.

What happens at the peak of the action potential?

Voltage-gated K+ channels open, and Na+ channels begin to inactivate.

Why does permeability to K+ increase slowly?

Because K+ channels are delayed rectifiers—they open more slowly in response to depolarization.

What causes repolarization after the spike?

K+ exits the cell, returning the membrane toward the resting potential.

How does the action potential transmit information in the nervous system?

By propagating a uniform electrical signal along the axon to the axon terminal, where it triggers the release of neurotransmitters.

Is the size of the action potential used to encode information?

No — the action potential is all-or-none and always the same size (about +35 mV). Information is encoded in the frequency of action potentials.

What does a higher frequency of action potentials indicate?

A stronger stimulus or more intense signal.

How does the action potential travel down the axon?

Through active propagation—voltage-gated Na+ channels open sequentially along the axon, regenerating the signal.

What ensures the one-way direction of an action potential?

The refractory period, especially the absolute refractory period, prevents the signal from going backward.

Where is the action potential (AP) initiated, and what happens during initiation?

• AP is initiated at the axon hillock.

• Na+ ions flow inward through voltage-gated Na+ channels.

• The inward Na+ current causes local depolarization of the nearby membrane.

• This depolarization triggers adjacent voltage-gated Na+ channels to open, propagating the AP down the axon.

How does the action potential propagate along the axon?

• Depolarization of the nearby membrane opens voltage-gated Na+ channels.

• The neighboring membrane reaches threshold.

• This new site becomes the next action potential initiation point, allowing the AP to travel down the axon.

Why does the action potential only travel in one direction along the axon?

• Na+ ions spread in both directions after an AP.

• However, the previous site is hyperpolarized due to K+ efflux and Na+ channels there are inactivated.

• This prevents depolarization and AP initiation backward, ensuring one-way propagation.

What mechanisms prevent the action potential from traveling backwards along the axon?

• Hyperpolarization of the membrane (due to K+ efflux) creates a refractory period.

• Inactivation of Na+ voltage-gated channels at the previous AP site.

• Together, these ensure the action potential only moves forward.

Does the voltage of an action potential change as it travels down the axon?

No, the action potential voltage remains constant as it moves down the axon. This is called non-decremental conduction, meaning the AP has the same size (amplitude) wherever it is measured along the axon.

How does action potential propagation occur along the axon?

Every part of the axon membrane sequentially undergoes changes in membrane potential and opening/closing of voltage-gated ion channels to propagate the action potential.

What factors enhance the speed of action potential conduction?

• Myelin sheath increases conduction speed by insulating the axon and enabling saltatory conduction.

• Larger axon diameter increases speed due to greater surface area for ion flow and reduced internal resistance.

Why are axons myelinated in the nervous system?

• Like insulating plastic on wires, myelin sheath insulates axons.

• This insulation improves the speed and efficiency of electrical signal transmission.

• Unmyelinated axons transmit signals slower.

How does myelin improve action potential transmission?

• Myelin acts as a high resistance insulator, preventing current leakage.

• This allows the action potential to "jump" between Nodes of Ranvier.

• This jumping is called saltatory conduction and speeds up signal transmission.

What is saltatory conduction and how does it affect signal speed?

• Saltatory conduction is the process where the action potential jumps from one Node of Ranvier to the next along a myelinated axon.

• This greatly increases signal speed:

  • Unmyelinated axons transmit at ~4 km/h

  • Myelinated axons transmit at ~400 km/h

How do the densities of Na+ channels compare between Nodes of Ranvier and myelinated regions?

• Nodes of Ranvier have about 10,000 Na+ channels per μm²

• Myelinated regions have only about 20 Na+ channels per μm²

This high density at the nodes supports saltatory conduction by regenerating the action potential.

What ions move through the Nodes of Ranvier during action potential propagation, and how do the Nodes and Myelin Sheath contribute?

• Na⁺ enters the axon at the Nodes of Ranvier through voltage-gated Na⁺ channels, causing depolarization.

• K⁺ exits the axon through voltage-gated K⁺ channels to repolarize the membrane.

• The Myelin Sheath insulates the axon, preventing current leakage and speeding up signal transmission by allowing the action potential to jump between nodes (saltatory conduction).

What is the difference between action potential propagation in myelinated vs. unmyelinated axons?

• Myelinated axons: Action potentials jump between Nodes of Ranvier where the membrane is exposed, in a process called saltatory conduction. Only nodes actively generate the AP.

• Unmyelinated axons: The action potential is generated continuously along every part of the membrane, leading to slower conduction.

What are the key points about action potential (AP) propagation?

• AP is all-or-nothing and non-decremental (does not lose strength).

• AP phases: depolarization, repolarization, and refractory period (hyperpolarization).

• Myelination and axon diameter increase AP conduction speed.

• Saltatory conduction is the jumping of AP between Nodes of Ranvier, caused by myelination.

What happens after the action potential reaches the axon terminals?

• The action potential triggers neurotransmitter release at the axon terminal.

• Neurotransmitters cross the synapse and bind to receptors on the postsynaptic neuron’s dendrites, transferring the signal.

What is the Rate Law in neuronal communication?

• Stimulus intensity is coded by the firing rate of the neuron.

• A more intense stimulus causes the neuron to spike more frequently.

• The frequency of action potentials determines how much neurotransmitter is released into the synapse.

• Different neurotransmitter concentrations cause different responses in the postsynaptic cell.

What happens during Synaptic Transmission when an action potential arrives at the axon terminal?

• Arrival of the action potential triggers influx of calcium ions (Ca²⁺) into the axon terminal.

• Calcium influx initiates a series of events that result in the release of neurotransmitters into the synapse.

How does calcium (Ca²⁺) influx at the axon terminal trigger neurotransmitter release?

• Ca²⁺ concentration is higher outside the neuron, so it flows inward down its concentration gradient.

• When an action potential arrives, voltage-gated Ca²⁺ channels open at the axon terminal.

• Ca²⁺ rushes into the neuron, triggering the release of neurotransmitter-filled vesicles into the synapse.

What role does calcium play in exocytosis at the synapse?

• Calcium entering the axon terminal releases neurotransmitter vesicles from protein anchors.

• It stimulates vesicle fusion with the cell membrane.

• This fusion causes exocytosis, releasing neurotransmitters into the synaptic cleft.

What happens during endocytosis and vesicle recycling at the synapse?

• After neurotransmitter release, excess membrane from vesicle fusion is pinched off.

• This forms new vesicles that can be refilled with neurotransmitter.

• This process recycles vesicles to maintain synaptic transmission.

What are the key steps in chemical synaptic transmission between neurons?

1. Action potential arrives at the presynaptic terminal.

2. Voltage-gated Ca²⁺ channels open, allowing Ca²⁺ to enter.

3. Ca²⁺ influx triggers vesicle fusion and neurotransmitter release into the synaptic cleft (~20–40 nm wide).

4. Neurotransmitter binds to receptors on the postsynaptic membrane, initiating a response.

Where does the neurotransmitter go after it is released into the synaptic cleft?

After release, the neurotransmitter can:

1. Bind to receptors on the postsynaptic neuron to transmit the signal.

2. Be broken down by enzymes in the synaptic cleft.

3. Be taken back up into the presynaptic neuron via reuptake transporters.

4. Diffuse away from the synaptic cleft.

What are axoaxonic synapses and their function?

Axoaxonic synapses occur between the axon of one neuron and the axon terminal of another.
They alter the amount of neurotransmitter released by the postsynaptic axon’s terminal buttons, often through activation of autoreceptors.

What are dendrodendritic synapses and their function?

Dendrodendritic synapses occur between dendrites of two neurons.
They help regulate the activity of groups of neurons and are often found in very small neurons that lack axons.
They can form electrical or chemical synapses, and may release neurotransmitters via exocytosis.

What is retrograde neurotransmission?

Retrograde neurotransmission is when the postsynaptic neuron sends signals back to the presynaptic neuron, often using lipid-based messengers like endocannabinoids or nitric oxide, to modulate neurotransmitter release.

What are electrical synapses and how do they work?

Electrical synapses occur via gap junctions, allowing direct, rapid transmission of ions and electrical signals between neurons.
They are faster than chemical synapses but less modifiable.

What is volume transmission in the nervous system?

Volume transmission is a type of neurotransmission where neurotransmitters or signaling molecules diffuse over a broader area, rather than being confined to a synaptic cleft.

What are the two main types of volume transmission?

1. Paracrine signaling – The signal affects neighboring cells.

2. Endocrine signaling – The signal (e.g., hormone) travels through the bloodstream to act on distant targets.

What is electrical communication via gap junctions?

It is direct electrical coupling between neurons through gap junctions, allowing ions to pass and synchronize activity between cells.

Where do electrical synapses typically occur?

They usually occur between dendrites of adjacent neurons.

What is a key feature of electrical synapses?

They are bi-directional, meaning membrane potential changes in one neuron affect the other.

What is one functional role of electrical synapses?

They can contribute to synchronized neuronal bursting or rhythmic firing patterns, such as those seen in some brain regions.

What is Wiring Transmission in the nervous system?

Wiring transmission refers to direct, targeted communication between neurons via synapses, where neurotransmitters are released into a narrow synaptic cleft and act on a specific postsynaptic receptor.

What is Volume Transmission?

Volume transmission is diffuse communication, where neurotransmitters or signaling molecules spread through extracellular fluid or cerebrospinal fluid to reach distant receptors, not confined to synaptic clefts.

How does the specificity of Wiring and Volume Transmission differ?

• Wiring Transmission is highly specific and localized.

• Volume Transmission is less specific, affecting multiple cells in a broader area.

What is Non-Synaptic Neurotransmission?

Non-synaptic neurotransmission refers to communication between neurons that does not occur across a traditional synapse, including mechanisms like retrograde signaling, volume transmission, and electrical synapses.

What is Retrograde Neurotransmission?

Retrograde neurotransmission occurs when the postsynaptic neuron releases signaling molecules (like endocannabinoids) that travel back to the presynaptic neuron to modulate neurotransmitter release.

What are Electrical Synapses and how do they work?

Electrical synapses use gap junctions to allow direct ionic current flow between neurons. This leads to fast, bidirectional communication and synchronizes activity between cells.