Action Potentials

three main ways to record electrical signals from the body

intracellular recording, extracellular recording, surface recording

intracellular recording

- one electrode is placed inside the cell and another is placed outside the cell.

- In this case the voltage difference between the two electrodes is the difference in voltage between the inside of the cell and the outside of the cell.

- This method is used to record action potentials

extracellular recording

- both electrodes are placed outside the cell.

- What is being measured is the voltage difference between two electrodes placed at different locations outside the cell.

- Using this method it is possible to measure a single action potential in a neuron, however the shape of the action potential will be different than the shape measured in the intracellular recording

surface recording

- the least invasive of all three types and is therefore used clinically.

- Electrodes can be placed anywhere on the surface of the body and one can measure the difference in potential between the two electrodes.

- in this case the electrodes are far away from the cells which they are measuring.

- In this case the electrodes are measuring the electrical activity of many cells.

Examples of surface recordings include

electrocardiography (ECG, heart), electroencephalography (EEG, brain), and electromyography (EMG, muscle)

excitable cells examples

neurons and muscle cells, heart, beta cells of pancreas

non-excitable cell examples

hepatocytes, lens cells, epithelial cells

excitable cells

can generate an action potential

MP in excitable cells is typically

negative, close to Nernst of K and Cl

excitable cells are mostly permeable to

K at rest, sometime Cl

electrical signalling in a neuron steps

1. postsynaptic membrane (often at a dendrite): ion channels open in response to the binding of a neurotransmitter, which is equivalent to injecting current into the neuron and causes the postsynaptic membrane depolarizes exponentially. This is referred to as the postsynaptic response.

2. The postsynaptic response propagates towards the axon.

3. If the postsynaptic response in the axon is large enough an action potential will fire in the axon.

4. the action potential travels down the axon towards its target cell (which could be a neuron, a muscle cell, a gland cell, or many other types of cells in the body).

5. Synaptic transmission occurs: chemicals diffuse across from one neuron to its neighbor and the process described above repeats

Release of transmitter from the presynaptic neuron results in? how does this occur?

the opening of ion channels in the dendrite

two ways it can occur

1. receptor for the NT is an ion channel. This is called an ionotropic receptor.

2. receptor for the NT is a G-protein coupled receptor, causes cascade that opens or closes an ion channel. This type of receptor is called a metabotropic receptor.

Examples of ionotropic receptor are

the glutamate receptor (a cation selective channel equally permeable to Na+ and K+) or the GABAA receptor (a chloride channel).

An example of a metabotropic receptor is the?

GABAB receptor which ultimately opens a potassium channel.

both cases of opening channels in the dendrite leads to?

current injection into the dendrite, causing the voltage to change exponentially

if positive current is injected into the dendrite

- the membrane potential rises exponentially from the resting membrane potential (Em) up to some value of voltage below threshold.

- when the stimulus is turned off (current no longer injected into the cell) the membrane potential decays exponentially back to the resting membrane potential.

ion channels in neurons do not open _____, but rather?

instantly, but rather over time dependent on the channel type

depolarizaton

membrane potential becomes more positive

exicatatory postsynaptic response

EPSP, postive charge injected into cell cause depolarization (MP becomes more positive)

increased membrane resistance causes

decreased open channels and decreased membrane surface area

decreased membrane resistance causes

increased open channels and increased membrane surface area

increased membrane capacitance causes

increased membrane surface area

decreased membrane capacitance causes

decreased membrane surface area

typical neuron time constant

10 msec

hyperpolarization MP

membrane potential becomes more negative

inhibitory postsynaptic response

IPSP, MP becomes more negative when injected with negative charge

Special Case: Depolarization of the postsynaptic response which generates an IPSP

- If the Nernst potential for chloride (ECl-) is more positive than the resting MP, then opening chloride channels will depolarize the membrane towards ECl-.

- However, since ECl- is more negative than threshold, opening chloride channels will prevent the membrane potential from reaching threshold because the opening of any other excitatory channels (Na+ for example) will have to overcome the effect of the open chloride channel

- In this sense chloride acts to buffer the membrane potential at ECl- and keep the membrane potential below threshold.

number of channels activated by neurotransmitter release will depend on

1. how much neurotransmitter is released

2. how long it stays in the synaptic cleft

3. how many receptors there are in the postsynaptic membrane

threshold

The voltage in a cell above which an action potential will be elicited and below which an action potential will not be elicited.

decision to fire an AP made at the

axon hillock

axon hillock integrates and decides?

the postsynaptic responses from all inputs, and based on that integration decides whether or not to fire an action potential

for most neurons, threshold is

10-20 mV above resting MP

categories of response at the axon hillock

1. a subthreshold response in which the response does not rise above threshold

2. a suprathreshold response which rises above threshold and initiates an action potential.

parts of an action potential

1. the postsynaptic response: an exponential rise above threshold.

2. the upstroke: the membrane potential rises from threshold quickly up close to the Nernst potential for sodium. During this phase the membrane potential is depolarizing.

3. repolarization: the membrane potential quickly falls back down close to the Nernst potential for potassium. During this phase the membrane potential hyperpolarizes.

4. the membrane potential depolarizes back slowly to the resting membrane potential.

voltage clamp

experimental tool that allows the study of the properties of the ion channels that are the basis for the action potential

During a voltage clamp, the experimenter:

1. Sets the voltage across the membrane of the cell to a specific value

2. Records the current through the channels present in the cell

types of ion channels that underlie the action potential

1. voltage gated sodium channels

2. voltage gated potassium channels

If the membrane potential is artificially set at -80 mV (near the normal resting membrane potential in an axon) then all of the sodium channels in the cell will be

closed and the current flowing through the sodium channels will be zero

If the membrane potential is artificially set to -60 mV some of the sodium channels will

open and the current through the membrane will increase. If the membrane potential stays at -60 mV then the sodium channels will close again (inactivated state)

If the membrane potential is artificially set to -30 mV more of the sodium channels will

open and the current through the membrane will increase even move than when the membrane potential was set to -60 mV. If the membrane potential stays at -30mV the sodium channels will inactivate

If the membrane potential is artificially set to a large positive value (+60 mV in this example), all the sodium channels in the membrane will

open and the current will increase to its maximum value. The sodium channels will then inactivate

If the membrane potential is artificially set at -80 mV (near the normal resting membrane potential in an axon) then all of the potassium channels in the cell will be

closed and the current flowing through the potassium channels will be zero.

If the membrane potential is artificially set to -60 mV some of the potassium channels will

open and the current through the membrane will increase. If the membrane potential stays at -60 mV then the potassium channels will not inactivate.

If the membrane potential is artificially set to -30 mV more of the potassium channels will

open and the current through the membrane will increase even more than when the membrane potential was set to -60 mV.

If the membrane potential is artificially set to a large positive value (+60 mV in this example), all the potassium channels in the membrane will

open and the current will increase to its maximum value

Voltage-gated sodium channels responsible for the ____ of the action potential have what two gates?

upstroke; An activation gate (C→O) and an inactivation gate (O→I)

activation gate

- opens in response to voltage

- more depolarized the membrane potential the greater will be the probability that this gate will open

- When this gate opens the channel moves from the closed state to the open state

inactivation gate

- not sensitive to voltage

- moves after the activation gate has opened the channel

- open channel provides an appropriate binding site for a tethered part of the protein to bind and occlude the pore

sodium gates summary

1. the activation gate of the sodium channel moves in response to membrane depolarization and opens the sodium channel

2. the inactivation gate plugs the pore of the channel almost immediately after the activation gate opens the channel and inactivates the channel

Voltage gated potassium channels involved in the ___ phase of the action potential have one gate, an?

repolarization; activation gate

voltage during the AP

Em

1. starts out at the resting membrane potential

2. depolarizes exponentially towards threshold

3. depolarizes rapidly towards the Nernst potential for sodium

4. hyperpolarizes rapidly towards the Nernst potential for potassium

5. slowly depolarizes back to the membrane potential

Permeability for Sodium (PNa+): ____ Feedback Loop

positive;

1. permeability for sodium is initially zero. All of the voltage-gated sodium channels are closed.

2. initial stimulus depolarizes membrane potential and opens some voltage-gated channels. The membrane permeability to sodium starts to rise.

3. influx of sodium through open voltage-gated channels depolarizes the membrane potential further and opens more voltage-gated sodium channels. Sodium permeability continues to increase.

4. after the sodium channels have opened the inactivation gate closes the channels. This decreases the membrane permeability to sodium back to zero

Permeability for Potassium (PK+): _____ Feedback Loop

Negative;

1. permeability for potassium is initially zero. All of the voltage-gated potassium channels are closed.

2. initial stimulus depolarizes membrane potential and opens potassium channels, but with a delay so that they open later than the sodium channels. The membrane permeability to potassium rises slowly and thus initially the open sodium channels primarily determine the membrane potential.

3. when enough potassium channels have opened the efflux of potassium through open potassium channels hyperpolarizes the membrane. This closes potassium channels and the membrane permeability to potassium decreases.

peak of the action potential occurs when?

the ratio of sodium permeability to potassium permeability is highest (much more sodium channels than potassium channels)

The most hyperpolarized potential during the AP occurs when?

the ratio of sodium permeability to potassium permeability is lowest (much more potassium channels than sodium channels)

depolarization

inside of cell becomes more positive

hyperpolarization

inside of cell becomes more negative

repolarization

- inside ofthe cell return to the resting membrane potential after the cell has either depolarized or hyperpolarized.

- However, it is most often used to describe the hyperpolarization part of the AP that occurs after the membrane has depolarized to a value close to the Nernst for sodium.

The density of voltage-gated sodium channels in most neurons is highest in the?

axon hillock

When a neuron is electrically stimulated, the axon hillock will be the first region to?

go above threshold, due to the high density of sodium channels.

- As a result, threshold in a neuron is primarily determined by the density of voltage-gated sodium channels in the axon hillock

A neuron with a higher density of voltage-gated sodium channels at the axon hillock (right) will have a?

lower threshold. This is because the neuron will more easily go above threshold due to the larger number of sodium channels at the axon hillock

how many refractory periods determine whether or not a ____ will happen?

2, second action potential can fire

absolute refractory period

- second action potential cannot fire during this time.

- Most of the sodium channels are inactivated.

- During this period not enough open Na+ channels can be recruited to fire an action potential (because most Na+ channels are inactivated)

relative refractory period

- A second action potential can fire during this time.

- However it requires a greater stimulus than normal to be elicited. This is because:

1. Some sodium channels are still inactivated.

2. Voltage-gated potassium channels are still open. This opposes any depolarization because open potassium channels cause the membrane potential to hyperpolarize and bring the membrane potential further away from threshold

amplitude of the action potential is relatively ___, determined by the?

constant; difference between the Nernst potential for sodium (maximum positive voltage of the action potential) and the Nernst potential for potassium (maximum negative voltage of the AP)

information in the brain is not coded by action potential amplitude, but rather by?

action potential frequency

maximum AP frequency possible is determined by the

absolute refractory period

using a reasonable value of about 1-2 msec for the absolute refractory period gives a maximum frequency of

500-1000 action potentials per second or 500-1000 Hz

physiologically, action potential frequencies up to ___ are observed

200-300 Hz

acetylcholine receptor: signal and channel

stimulus

stretch/ligand/voltage gated

stimulus

- when neuron is stimulated ion channels open and current is injected into the cell = postsynaptic response.

- Physiological examples of stimuli include such external stimuli as heat, odors, food (taste).

- One common response is the opening of a cation selective channel. This will depolarize the cell.

subthreshold response in an excitable cell

if the current injected as a result of a given stimulus does not produce a voltage change large enough to reach threshold or there are no voltage-gated sodium and voltage-gated potassium channels, the signal will decay in amplitude as it travels down the axon

suprathreshold response in an excitable cell

If the current injected as a result of a given stimulus produces a voltage change large enough to reach threshold the signal will travel down the axon without a decay in amplitude.

because the action potential is regenerated at each successive segment of the axon, and since the Nernst potential for sodium determines the ___ of the action potential, the ___ is always the same which allows the action potential to?

height; height of the signal; travel long distances, for example from the head to the foot, without a decay in the signal.

suprathreshold AP cannot

travel backwards because the region that was just excited is now in its refractory period

size of the signal will decrease due to two factors:

1. loss of ions through the membrane to the outside of the axon, determined by the membrane resistance (Rm).

2. loss of energy to heat due to the cytoplasmic resistance through collisions, determined by the cytoplasmic resistance (Rc)

As the postsynaptic response propagates from the ___ to the ____, the height of the postsynaptic signal (deltaV) will gradually?

dendrite; axon hillock; decrease due to the loss of ions across the membrane (Rm) and due to loss of energy due to cytoplasmic collisions (Rc)

length constant

V(x) = V0 e^(-x/λ)

V(x): voltage at x along the axon

Vo: size of the initial signal

λ: length constant

x: distance down the axon.

a short length constant means that the?

size of the signal decreases more a given distance from the initiation of the signal.

a long length constant means that the?

size of the signal decreases less over a given distance from the initiation of the signal

the length constant depends on

1. the membrane resistance (Rm): the higher the membrane resistance the less charge leaks out from the neuron and there will be a smaller decrease in the height of the signal.

2. the cytoplasmic resistance (Rc): the higher the cytoplasmic resistance the more energy is lost to heat (molecular collisions give off heat) and the height of the signal will decay at a faster rate.

length constant: change in cytoplasmic resistance

increase: decrease of diameter of axon

decrease: increase of diameter of axon

length constant: change in membrane resistance

increase:

- decrease in open ion channels

- decrease in membrane SA

- increase in membrane thickness

decrease:

- inc in open ion channels

- inc in membrane SA

- dec in membrane thickness

Typical length constant values for neurons are?

hundreds of microns (100 um).

A change in diameter of the axon will change both the?

membrane resistance (by changing the surface area of the axon) and the cytoplasmic resistance (by changing the cross-sectional area of the axon)

TIME CONSTANT VERSUS LENGTH CONSTANT

time constant describes the rate of change of voltage across the membrane at a particular location in the membrane whereas the length constant describes the rate of decay of the signal along the neuron.

propagation of an AP

1. A stimulus initially injects current into the axon

2. this depolarizes the membrane, opens voltage-gated sodium channels, and triggers an action potential

3. the opening of voltage-gated sodium channels allows positively charge sodium ions to enter the axon.

4. the sodium ions travel through the cytoplasm and depolarize an adjacent axon membrane

5. this depolarization opens up voltage-gated sodium channels in the adjacent membrane and triggers and action potential in the adjacent membrane

- Steps 3-5 are repeated as the action potential travels down the axon

if an axon was stimulated somewhere in the middle (i.e. somewhere between the two ends of the axon) then the action potential would?

travel in two directions away from the stimulus.

the velocity of propagation of an action potential is related to the time constant how?

inversely proportional, For a large time constant the adjacent membrane will take longer to reach threshold

the velocity of propagation of an action potential is related to the length constant how?

proportional, For a larger length constant more adjacent membrane will reach threshold. Thus the signal will move faster down the axon

length constant equation

LC= (Rm/Ra) ^1/2

LC= length constant

Rm= membrane resistance

Ra= axial resistance

time constant equation

T=Rm x C

velocity equation

v = length constant/ time constant

An increase in the membrane resistance changes what and how?

increases the time to charge up adjacent membrane and thus will decrease the velocity of the action potential

The higher the cytoplasmic resistance the more ____ it is for the action potential to?

difficult; move down the axon: therefore the lower the velocity of the action potential

An increase in membrane capacitance increases the?

time to charge up adjacent membrane and thus will decrease the velocity of the action potential.

main physiological mechanisms to change the velocity of an action potential:

1. axon diameter:↑ axon diameter → ↑ velocity. An increase in axon diameter increases the velocity of an action potential by decreasing the cytoplasmic resistance (Rc). This increases the length constant and essentially makes it easier for the electrical signal to travel down the axon.

2. myelination:↑ myelination → ↑ velocity. As discussed below, myelination increases the velocity of an action potential mainly by decreasing the capacitance but also by increasing the amount of insulation surrounding an axon

myelin

layers of schwann cells that wrap around an axon

myelin is equivalent to

increasing the thickness of the axon membrane

nodes of ranvier

interruptions in myelin every 1-2mm, resulting in gaps of 2um with no myelin