Neuroscience: Cable Properties of Neurons & Graded Potentials

Describe transient depolarization.

(Top Example) If a larger stimulus is applied, we see a larger response in the cell. If we increase the duration of the stimulus, we see an increase in the duration of the response.

What are 3 properties that distinguish graded potentials from action potentials?

1. Graded potentials exhibit a response proportional to the stimulus 2. Graded potentials exhibit electronic conduction 3. Graded potentials are decremental One more: • Graded potentials propagate bidirectionally • Axon potential are unidirectional.

What are the 3 Events that are triggered at Threshold?

1. Sodium channels activated - Immediate 2. Potassium channels activated - Delayed 3. Sodium channels inactivated - Delayed All 3 are triggered simultaneously, the only difference is the time it takes for the channels to open and inactivate (kinetics)

What is spatial summation?

A cell can be stimulated at multiple times, but also in multiple places. When a potential has to travel far distances, it loses amplitude. However, if multiple synapses are firing at the same time, in different places, summation occurs. When several synapses add, it might be enough to generate an action potential. Summation can occur both over space and time. The space constant is important in determining spatial summation.

Which line represents a pure capacitor?

A linear line going up. It is important that you understand the capacitance has a influence on the the shape and how long it takes.

What are the two types of refractory periods?

Absolute and Relative

What is the difference between Absolute and Relative refractory periods?

Absolute: • No AP can be generated • Due to Na⁺ channel inactivation Relative: Requires more stimulation to overcome it. • Time after AP where a new AP is possible but difficult because it requires greater depolarization • Due to leaky K⁺ current and undershoot

Review Saltatory Conduction.

Again, it jumps from node to node.

What happens ahead of the action potential in an axon?

Ahead of the action potential begins to reach threshold.

What is required to created an action potential?

Almost all action potentials require many neurons to summate except neuromuscular (due to ACH). Graded potentials are sub‐threshold potentials that do not generate action potentials. Summation can lead to the neuron reaching threshold and firing an action potential.

What is the membrane potential at rest?

Around -70 mV

What happens at the peak of an action potential?

At the peak of the rising phase, the membrane is closer to the Nernst potential for sodium, due to the delayed opening of the K⁺ channels and inactivation of Na⁺ channels. Absolute brake= inactivation of Na+ channels.

What is the effect of myelination on Rm & Cm? Why?

Axon myelination increases Rm and decreases Cm • No channels in myelin • Electrostatic attraction depends on distance, but the myelin increases the distance between the charges so they cannot be stored • Spacing the nodes will increase the rate of propagation • Electronic conduction in between nodes

Why is the membrane not a perfect capacitor?

Because it has channels in it. So it is leaky capacitor. Therefore, current is always leaking through it. In that respect, it does not act as a perfect resistor either

Why don't action potentials go backward once it has begun?

Because it is in its refractory period.

Why is the lipid bilayer a good capacitor?

Because the ions line up at the membrane but can't pass through without a channel. This stores charge at the membrane, creating an electrostatic interaction. This is very stable, which resists changes in charge. Since the membrane is so thin, when current flows it is not going to instantaneous change the distribution of the charge because the are very stably stored there by the distribution of electrical charges.

What is Depolarization?

Becomes more positive - True depolarization only happens until potential equals 0. After 0 it is said to be repolarizing in the opposite direction.

How is the firing rate of a neuron determined?

By absolute refractory period.

How can axons change Axial resistance?

By having different diameters.

What are the diseases of myelination?

CNS: MS (Multiple Sclerosis) - Oligodendrocytes PNS: Guillain-Barré syndrome - (Schwann Cells)

What pathways are not myelinated?

Chronic pain pathways don't need to transmit as fast, therefore usually aren't myelinated

What are the two type of conduction?

Continuous and Saltatory conduction

Is Depolarization instantaneous?

Depolarization is not instantaneous. It is more like the top picture. The membrane lags a little bit when reaching maximum depolarization, as well as when it returns to threshold. The time it takes for a neuron to reach maximum potential is called the time constant. If it was instantaneous, then it would look like the bottom picture.

What is Space Constant?

Distance by which a stimulation decays by 63%. Determines how far the depolarization will travel down the axon. Does not take time or rate into account!!!

What is Repolarization?

Down to Resting Membrane Potential.

Why are there differing refractory periods?

Due to different Na⁺ channels. NOTE: Magnitude does not change, but frequency does. In the image, these are two different neurons responding differently to the same stimulus due to the different Na⁺ Channels. • Cell 1 has a shorter refractory period so it resets quicker so it fires at a quicker frequency. • Cell 2 has a longer refractory period.

What pathways are myelinated?

Fast conduction needed for many somatic reflexes and smooth coordinated movements • Myelin takes up a lot of space, so brains would be HUGE if all neurons were myelinated • Myelin is energetically expensive

How does fewer ions effect capacitance?

Fewer ion channels (fig, A) equals more capacitance due to greater ability to store charge.

Compare Graded Potentials to Action Potentials?

Graded Potentials • Dimmer Switch • Multidirectional • Decremental • Summate over space and time Action Potentials • All or none • Unidirectional • Non-Decremental • No Summation

Describe how Graded potentials are decremental?

Graded potentials are decremental because the signal decays. Action potentials do not diminish with distance (regenerative) In other words, the farther from the site, the lower the signal becomes. Eventually it dampens to nothing. Axon potentials are meant to go long distances so they do not die out.

How is more action potentials coded in the system?

Higher Frequency So if you push on sensory receptor lightly it may generate a few action potentials. However, if you push harder, that will generate more action potentials at a higher frequency. That is how the body encodes sensory information. It encodes it in frequency of action potentials. As you increase in intensity, the frequency of action potentials increase. If you increase the frequency of action potential, it will increase the amount of neurotransmitter released from that neuron. That will increase the amount of neurotransmitter released in the entire pathway. That will influence the next neuron and so forth.

What does this mean? How does a change in the number of ion channels effect the membrane potential?

If both neurons are stimulated in identical ways, the membrane response will be different. Both will depolarize to the same level, but Fig. A will be slower but exhibits temporal summation.

What are the two paths that current can take?

It can travel down the cytoplams or it can leak through the membrane.

What is the purpose of the refractory periods?

It ensures that after an action potential is generated that it can't generate another action potential for a certain amount of time. So, the membrane is insensitive to further stimulation.

Describe how graded potentials exhibit electronic conduction.

It is a type of passive conduction. The membrane depolarizes in a bidirectional fashion (i.e. depolarization spreads in both directions from the stimulus, not just in the spot where the stimulus was applied). Bidirectional propogation is not an intrinsic feature of action potentials in an axon. Action potentials are unidirectional under normal circumstances.

How is Conduction velocity calculated?

It is change in distance/change in time, measured in meters/second. =∆d/∆t

Why is increased frequency in a presynaptic neuron important?

It is important for determining how much neurotransmitter is released

What is Axial resistance?

It is resistance to flow of ions along the cytoplasm. During an action potential when Ion channels open up and sodium starts coming in, the + ions don't just sit there they diffuse along both forward and backwards along the axon.

What will a larger diameter axon do to Ra?

It will decease Ra, which will speed up CV since it is inversely proportional. Like water passing through a hose. The smaller the hose the higher the Ra. Inverse is true, the larger the diameter the lower Ra. So more room, for more diffusion and less cytoplasmic collision so it goes faster.

What is myelination effect on Rm?

It will increase Rm due to the reduction in channels. Myelin reduces the number of channel to diffuse which will increase Rm.

How would a decrease concentration of ion channels effect space constant?

It will increase membrane resistance which will increase the space constant. So less leakage across the membrane.

If a neuron has increased capacitance, what will happen time constant?

It will increase the time constant.

Which line represents a pure resistor?

It would be more of a square wave. So when a stimulus was applied, you would see an instantaneous change in membrane potential.

What if the neuron was stimulated on the axon what would occur?

It would then be bidirectional; however, the axoaxonic synapses are usually inhibitory. Inhibitory axons hyperpolarize the membrane. Usually the axoaxonic synapses are close to the hillock.

How is time constant calculated?

Membrane resistance x membrance capacitance = time constant Two seperate properties, but they both interact to determine time constant. Therefore, as either of them go up, the time constant will increase.

How does more stimulus effect the action potential?

More stimulation causes more action potential to generate.

What are the mechanisms for speeding up conduction velocity?

Myelination and size of axon

Describe temporal summation.

Notice in both figures, both depolarize the same but one has a higher time constant than the other. If it responds too quickly, then it will get to baseline quickly. Then, when the same stimulus comes again, it gets the same response. But a longer time constant, it has not fully repolarized so the same stimuli can cause summation.

What is the Passive (electronic) conduction rate to RaCm? Why?

Passive (electronic) rate is inversely proportional to RaCm. If the membrane is storing charge, it will resist change and conduct slower

What are the two types of conduction?

Passive and Active conduction.

What is the difference between Passive and Active conduction.

Passive conduction (graded potentials) = electronic conduction • Bidirectional • Decremental Active conduction = continuous or salutatory conduction • AP propagation • Unidirectional • Non‐decremental

What is responsible for relative refractory period? Why is the neuron less excitable?

Potassium channels close slowly so even after the membrane resets, it is still leaky to potassium. Therefore, any depolarizing stimulus will need to be larger than before to counteract the leaky potassium.

What happens when threshold is reached?

Reaching threshold triggers the opening of voltage gated Na⁺ channels. This is called a "Molecular switch" = depolarizing the membrane enough so that the voltage gated Na⁺ channels open.

Does a small diameter axon or large diameter axon have a higher Axial resistance?

Smaller has a higher resistance. Like a water hose, the smaller the tube, the higher the resistance.

The interaction of both membrane resistance and axial resistance interact to determine what constant?

Space Constant

Why not myelinate all neurons?

Speed is not always the most important thing. Speed also takes up a bunch of space so only important pathways are myelination.

What determines the upper limit of frequency for an action potential?

The absolute refractory period

What happens as the action potential move down the axon?

The action potential really just gets renewed at each section of the axon. It is a pretty slow process. Each section needs to open channels and such to let sodium in.

How does the membrane create a lag time for the time constant?

The cell membrane acts as both a capacitor and resistor, which creates the lag time for the time constant.

Describe how graded potentials exhibit a response proportional to the stimulus.

The hallmark characteristic of graded potentials is that they are graded in their intensity i.e. the response is proportional to the stimulus. An Action potential is either all or none. Graded are more like a dimmer switch and Action potential is an on/off switch.

What predicts the initial slope as well as the down slope?

The initial slope is predicted by the capacitor properties, whereas the down slope is predicted by the resistor properties.

Why does myelination reduce capacitance?

The myelin increases the distance between the charges so they cannot be stored. What makes a capacitor? It has to be thin. It is very narrow that allows the attractions to be intense. That will decrease the speed. However, with myelination, that increases the distance with fatty myelin between the ECF and ICF. This increases the length that the charges have to interact. As they are moved farther away, they have a decrease in capacitance. So essentially, myelination breaks up capacitance which will speed it up.

What is the difference between fig, A and fig, B in the image?

The number of ion channels.

What is Hyperpolarization?

The resting membrane potential becomes more negative than normally (undershoot).

Myelin speeds up the action potential, but what if there where no breaks in the myelin?

The signal would fade out. That is why it is important to have the Nodes of Ranvier to regenerate the signal.

What is Capacitance?

The storage of charge across barrier

Define time constant?

The time it takes for the membrane to depolarize to 63% of its max level.

What happens to threshold as excitability goes up?

Then the threshold goes down. It becomes easier to hit threshold. So, threshold gets easier to reach the longer it goes through the refractory period.

Review a unidirectional AP.

They do not dampen out as they travel down the axon.

As the axons gets bigger, what happens to the space between the nodes?

They get farther apart. More myelination increase Rm which has an effect on Time Constant. In turn, that will increase the length constant which means it can go farther before decaying. So the booster signals can be spaced farther apart.

Why do action potentials not summate?

This is due to the refractory periods.

What is the fundamental machinery at the nodes for propagating an AP?

Voltage gated Na⁺ Channels. They appears at the nodes of Ranvier.

What happens to the space constant if we increase axoplasmic resistance (Ra)?

We decrease the distance. Rm and Ra are inversely proportional.

What happens to the space constant if we increase membrane resistance (Rm)?

We increase the the space constant.

Describe Saltatory conduction.

• AP jumps from node to node • This process is faster because the AP is only generated at the node of Ranvier instead of along the membrane (continuous conduction) • Na+ channels are concentrated at the nodes • Graded potentials in between nodes • Spaced out nodes= increases length constant and distance the AP's jump → faster conduction

What is the effect of increased ion channels?

• It will decrease the resistance which in turn will decrease the time constant. • Fig. A has greater resistance due to fewer channels. • Therefore, the time constant is higher for Fig. A than Fig. B

What are the variables that will affect Axial resistance?

• Length of pathway (axon length) - the longer the length the higher the resistance. • Cross‐ sectional area (axon diameter)

Describe Continuous conduction.

• Non‐myelinated neurons • Constant regeneration in adjacent membrane • Slow way to move forward due to time it takes to open channels • AP propagation starts at axon hillock, if the AP was generated distally we COULD get bidirectional propagation, but this does not take place in the body.

What are the two ways that an action potential can propagate down an axon?

• Salutatory conduction • Continuous conduction Will talk more about it later.