Physio 4) Neuronal Conduction

What is the overall sequence from receiving a signal to sending an action potential?

Neurotransmitter/input at dendrites
→ graded potential
→ graded potential spreads toward soma/axon hillock
→ if membrane reaches threshold
→ action potential begins
→ AP travels down axon
→ reaches axon terminal and can trigger neurotransmitter release.

What is depolarization vs hyperpolarization?

Depolarization: membrane becomes less negative. shifts toward ENa +60mV.
Hyperpolarization: membrane becomes more negative. shifts toward Ek -90mV

Which ion movements commonly produce depolarization and hyperpolarization?

Na⁺ influx → depolarization
K⁺ efflux → hyperpolarization

What is a graded potential?

A local, modest change in membrane potential whose size depends on stimulus strength.

It may be:

• depolarizing

• hyperpolarizing

Where do graded potentials usually occur in neurons?

Mainly in the dendrites and cell body/soma, which receive input from other neurons.

What happens to a graded potential as it travels away from its origin?

It decays with distance.

So:

strongest near stimulus → progressively weaker farther away.

What determines the size of a graded potential?

The strength of the stimulus.

Stronger stimulus → larger graded response.

What physiological role do graded potentials have?

They serve as local signals that increase or decrease neuronal excitability and can trigger an AP if they depolarize the axon hillock to threshold.

What does it mean that graded potentials can summate?

Multiple graded potentials can add together, making the membrane more or less likely to reach threshold.

What is the main role of the axon?

The axon carries the neuron's output signal, usually as an action potential, toward the terminal branches.

Where does the axon begin?

At the axon hillock.

The axon can be very long, and the lecture notes that in some animals it can extend several meters.

What is the main role of dendrites and the soma?

They are the major receptive surfaces of the neuron and receive inputs from other neurons.

Graded potentials usually spread through these regions.

What is myelin and what does it do?

Myelin is a fatty whitish insulating sheath wrapped around many axons.

It insulates the axon from the surrounding solution and greatly increases conduction velocity.

What are nodes of Ranvier?

Gaps in the myelin sheath where the axonal membrane is exposed to extracellular fluid.

These are the sites where action potentials are regenerated during saltatory conduction.

Stimulating vs recording microelectrode?

Stimulating microelectrode → injects current to change membrane potential and can trigger a graded or action potential.
Recording microelectrode → measures the resulting membrane potential at a location in the neuron.

What happens if a depolarizing stimulus is subthreshold?

It produces a graded depolarization but no action potential.

Compare graded potentials and action potentials.

Graded potentials

• variable amplitude

• can summate

• no fixed threshold required

• decay with distance

• duration varies

• can depolarize or hyperpolarize

Action potentials

• all-or-none

• require threshold

• do not decay with distance

• fixed amplitude under given conditions

• have refractory periods

• begin with depolarization

What does “all-or-none” mean?

Once threshold is reached, a full AP is generated.

A stronger suprathreshold stimulus does not produce a taller AP.

What is excitability?

The ability of a cell to fire an action potential.

What is threshold?

The membrane potential that must be reached to trigger an AP.

The lecture states it is usually about 20–30 mV above RMP.

What happens when membrane potential reaches threshold?

Fast voltage-gated Na⁺ channels open rapidly.

Na⁺ influx increases dramatically
→ regenerative depolarization
→ full AP.

Where does the transition from graded potential to action potential usually occur?

At the axon hillock/initial segment.

This area has a high density of fast voltage-gated Na⁺ channels.

What is the typical sequence from an excitatory synaptic input to an AP?

Excitatory neurotransmitter
→ dendritic graded depolarization
→ spreads toward axon hillock
→ reaches threshold
→ AP generated
→ AP travels down axon

What does an inhibitory neurotransmitter usually do?

It produces local hyperpolarization, making threshold harder to reach.

What are the main phases/components of an action potential?

1. depolarization/upstroke

2. overshoot

3. repolarization

4. after-hyperpolarization/undershoot in some cells

What is overshoot?

The portion of the AP where membrane potential becomes positive, above 0 mV.

What is after-hyperpolarization/undershoot?

The phase when membrane potential falls below the resting membrane potential after repolarization.

Not every excitable cell shows a clear undershoot.

What causes the rising phase of the action potential?

Rapid opening of fast voltage-gated Na⁺ channels.

Na⁺ moves inward
→ positive charge enters
→ rapid depolarization.

What happens to Na⁺ conductance and resistance during depolarization?

Na⁺ channels open
→ Na⁺ conductance increases

Because:

g=1/R

Na⁺ resistance decreases.

Toward what equilibrium potential does Vm move during the upstroke?

Toward:

The lecture's AP peak is around +35 mV.

Does Vm actually reach ENa at the AP peak?

No.

It approaches ENa, but Na⁺ channels begin to inactivate and K⁺ conductance rises before Vm reaches ENa.

Does an AP require a huge movement of ions across the membrane?

The important lecture point is that AP generation reflects ion flux through voltage-gated channels, especially Na⁺ inward during the upstroke.

What causes the falling phase/repolarization?

: Two major events:

1. fast Na⁺ channels become inactivated

2. voltage-gated K⁺ channels open

K⁺ flows outward
→ positive charge leaves
→ membrane repolarizes.

What happens to Na⁺ conductance and resistance during repolarization?

Na⁺ channels inactivate
→ ↓ Na⁺ conductance
→ ↑ Na⁺ resistance

What happens to K⁺ conductance and resistance during repolarization?

K⁺ channels open
→ ↑ K⁺ conductance
→ ↓ K⁺ resistance

What are the directions of Na⁺ and K⁺ flux during the AP?

Depolarization: Na⁺ moves inward

Repolarization: K⁺ moves outward

Why can after-hyperpolarization occur?

K⁺ channels close slowly, so K⁺ continues leaving after the membrane has repolarized.

Vm moves toward:

EK≈−88 to −90 mV

producing the undershoot.

What happens as after-hyperpolarization ends?

K⁺ channels close
→ K⁺ conductance falls
→ outward K⁺ flux decreases
→ Vm returns toward RMP.

The lecture also notes that Ca²⁺ flux can contribute to after-hyperpolarization.

What are the two gates of a fast voltage-gated Na⁺ channel?

• activation gate

• inactivation gate

What are the three functional states of the fast Na⁺ channel?

Resting: activation gate closed; channel can be activated

Open: activation gate opens → Na⁺ enters

Inactivated: inactivation gate closes → Na⁺ influx stops

The channel must recover back to resting state before it can fully open again.

What is the absolute refractory period?

The period during which no second AP can be generated, regardless of stimulus strength.

This occurs while Na⁺ channels are open or inactivated.

What is the relative refractory period?

The period when a second AP can occur, but only with a stronger stimulus.

Some Na⁺ channels have recovered, but:

• some remain inactivated

• K⁺ conductance is still high

• membrane may be hyperpolarized

What is the approximate duration of the refractory periods in the lecture?

Absolute refractory period:
<1 ms

Relative refractory period:
approximately 3 ms

What is the physiological importance of refractory periods?

They:

• help ensure unidirectional orthodromic conduction

• limit maximum firing frequency

• reduce the likelihood of excessively rapid neuronal discharge/seizure activity

How do local anesthetics stop action potential conduction?

They block voltage-gated Na⁺ channels.

No adequate Na⁺ influx
→ no normal depolarization
→ no AP propagation
→ nerve conduction is blocked.

How do phenytoin and carbamazepine affect Na⁺ channels?

They prolong the inactivated state of voltage-gated Na⁺ channels.

This prolongs refractoriness and reduces repetitive neuronal firing.

How does an action potential propagate in an unmyelinated axon?

INa⁺ enters one segment of membrane
→ local current depolarizes the adjacent segment
→ nearby voltage-gated Na⁺ channels open
→ a new AP is generated there.

So the AP moves segment by segment along the axon.

What two factors increase action potential conduction velocity

1. Larger axon diameter

2. Myelination

Lecture speeds:

• Myelinated axons: 2–100 m/s

• Typical unmyelinated axons: 0.1–1.5 m/s

What is saltatory conduction, and why is it faster?

Saltatory conduction is AP conduction in myelinated axons, where the signal is regenerated mainly at the nodes of Ranvier.

Myelin insulates the internodes
→ current spreads rapidly to the next node
→ AP is regenerated at the node
→ signal appears to “jump” node to node.

Nodes contain a high density of fast voltage-gated Na⁺ channels.

How does demyelination impair conduction, and what diseases are examples?

Loss of myelin causes current to leak out through damaged membrane instead of efficiently reaching the next node.

→ conduction slows or can fail completely.

Examples:

• Multiple sclerosis = CNS

• Guillain-Barré syndrome = PNS

Why can hyperkalemia cause muscle weakness?

Hyperkalemia causes sustained depolarization
→ more fast Na⁺ channels remain inactivated
→ refractory period increases
→ fewer Na⁺ channels are available
→ excitability falls
→ muscle weakness.