Cellular Neurophysiology

Question 1

What does excitatory mean?

Answer 1

The potential is moving closer to the threshold.

Question 2

What does inhibitory mean?

Answer 2

The potential is moving further away from the threshold.

Question 3

What are local potentials and what are there key properties?

Answer 3

Local potentials are small changes in the membrane potentials as a result of ions crossing the membrane. They occur at the dendrites/cell body.

They are graded in size, decreases in amplitude over distance, the summate in time and space, they can depolarise or hyperpolarise, and they influence the generation of an action potential.

Question 4

What is the plasma membrane and its composition?

Answer 4

The plasma membranes a barrier to the free movement of ions.

The plasma membrane is made up of a phospholipid bilayer which has water loving hydrophilic heads and hydrophobic tails. Because of this for ions to pass through the membrane they must go through a channel or travel with a carrier.

Question 5

What is a chemical gradient?

Answer 5

The energy provided by the difference in concentration across the plasma membrane.

Question 6

What direction do ions move?

Answer 6

From area of high concentration to low concentration.

Question 7

What is a electrical gradient?

Answer 7

The energy associated with moving charged molecules across the membrane - when a membrane potential exists.

Question 8

What is the electrochemical gradient?

Answer 8

An electrochemical gradient is the chemical gradient plus the electrical gradient.

The electrochemical gradient determines the direction that ions will flow through an open channel and is determine by using the Nernst equation.

Question 9

What is the relevant concentrations of sodium, chloride and potassium from inside of the cell to outside of the cell.

Answer 9

High sodium and chloride outside the cell, low potassium.

Low sodium and chloride inside the cell, high potassium.

Question 10

What is equilibrium?

Answer 10

Where there is an equal number of ions leaving and entering (not when gradients are equal). Equilibrium is about movement.

Question 11

Why do we need to use the Ernest equation?

Answer 11

Because the chemical and electrical gradients can be in conflict (e.g., Potassium). Therefore we need to work out the overall potential of the single ion to determine where the ion wants to go.

Question 12

What is depolarisation?

Answer 12

Depolarisation is when the membrane potential becomes less negative (more positive) e.g., moving towards zero.

From threshold to 0mV.

Question 13

What is repolarisation?

Answer 13

Repolarisation is when the membrane potential becomes more negative e.g., moving away from zero.

From 0mV to threshold.

Question 14

What is the absolute refractory period and why does it occur?

Answer 14

The time where you cannot generate another AP at that cell due to the inactivation of voltage sodium channels meaning that they do not respond to their environment.

Inactivation is caused by the “ball” blocking the end of the open pore.

After a period of time the ball automatically moves and the channels are now just closed and can be opened again in respond to their environmental changes.

It is due to the refractory periods that action potentials cannot propagate backwards.

Question 15

What is a relative refractory period?

Answer 15

The period during afterhyperpolarisation where you can generate another AP but the potential is further from zero than the RMP so it requires a greater stimulus than normal (therefore more difficult to initiate).

Question 16

What is a AP overshoot?

Answer 16

The overshoot is the point where the action potential passes 0mV.

Question 17

What is conductance and what does it depend on?

Answer 17

Conductance is the measure of how many ions cross the membrane.

It depends on the permeability of the membrane (e.g., channels) and the equilibrium potential of the membrane (whether or not there is a driving force).

Question 18

What causes voltage-gated ion channels to open?

Answer 18

A change in the voltage of the membrane = depolarisation.

Question 19

What are three key blockers of Voltage-Gated sodium channels?

Answer 19

Tetrodotoxin (irreversible)
Saxitoxin
Lidocaine (short acting)

Question 20

What are the three stages of a voltage gated ion channel and what is happening at each

Answer 20

Open - pores are open allowing for positivity charges ions to cross the membrane.

Closed - pores are closed and therefore positively charged ion cannot cross the membrane.

Inactivation - pores are open but channel is blocked by the ball at the end.

Question 21

What is the key difference between voltage gated sodium and potassium channels (other than their selectivity)?

Answer 21

Potassium channels have slower kinetics than sodium channels.

A sodium channel is normally closing as a potassium channel is opening - it is the opening of potassium channels that drives repolarisation.

Question 22

Why is it harder to create an AP during the relative refractory period?

Answer 22

Because there is an increase quantity of potassium permeability causing the membrane potential to be further from threshold.

Question 23

Why can AP not move backwards?

Answer 23

Refractory periods.

Absolute refractory period due to the placement of the inactivation ball.

Plus during relative refractory period it is more difficult to initiate an AP.

Question 24

What effects the speed of conduction along an axon and why?

Answer 24

The axon diameter because a bigger axon allows more through.

Myelination because it reduces current leak and creates saltatory conduction.

Question 25

What is saltatory conduction?

Answer 25

Saltatory conduction is created by myelination.

It is the enhance speed of conduction between nodes due to there being no channels in the internodes but a very high density of channels at the nodes allowing the depolarisation to transfer over nodes.

Question 26

What are the characteristics of electrical synapse’s?

Answer 26

Very fast
Ions flow from cell to cell
Can be opened by voltage, pH, Ca2+ and receptors

Question 27

What are the characteristics of Chemical synapse’s?

Answer 27

Slower
Rely on chemical crossing the gap
Complex series of events
Neurotransmitters packaged in vesicles
Synapse strength can be modified

Question 28

Are chemical or electrical synapses faster?

Answer 28

Electrical

Question 29

What is the difference between gaseous transmitters and neurotransmitters?

Answer 29

Gaseous transmitters can diffuse across the membrane and directly into other cells. Whereas, neurotransmitters must bind to receptors to enter into cells.

Question 30

What is Exocytosis?

Answer 30

The fusion of vesicles to the plasma membrane and the release of neurotransmitters into the synaptic cleft.

Question 31

What is the process that occurs once an action potential reaches the synapse?

Answer 31

The depolarisation of the AP activates the voltage gated calcium channels and calcium enters the synapse. The calcium activates alot of things including the movement of vesicles to the membrane where they undergo exocytosis. The release of neurotransmitters activates receptors.

Question 32

What prevents the plasma membrane from exponentially growing by the process of exocytosis?

Answer 32

Recycling (creating new vesicles from the membrane). Plus there is not only full fusion there is also partial fusion through the “kiss and run” process.

Question 33

What is temporal summation?

Answer 33

Summation between the EPSP from the same input that occur close enough together in time

Question 34

What is spatial summation?

Answer 34

Summation between events that occur close enough together in space from different inputs - still requires them to be close in time.

Question 35

What is synaptic modulation?

Answer 35

Changes to the magnitude of the response due to change in the synapse itself.

Question 36

Describe Gaseous Neurotransmitters

Answer 36

Gaseous transmitters diffuse out of cell of origin and directly into other cells. They can act inside cell of origin or in cells distant from point of release.

They do not require receptors.

Question 37

What neurotransmitter class does glutamate belong to?

Answer 37

Small Molecule - Glutamate is an excitatory amino acid.

Question 38

What are the features of classic neurotransmitters (class, storage and receptors)?

Answer 38

Small Molecules

They are stored in vesicles (which undergo exocytosis - either full or partial).

They act on ionotropic and G-protein coupled receptors (GPCR).

Question 39

What are ionotropic receptors?

Answer 39

Ionotropic receptors are post synaptic membrane receptors that function as ligand gated ion channels. Once a neurotransmitter bind to the receptors they open to allow ions to flow across the membrane.

When the ligand (neurotransmitter) is not bound the channel is closed.

Question 40

What are G-Protein coupled receptors?

Answer 40

Also referred to as matabotropic receptors.

GPCR are a receptor associated with a G-protein (three subunits = alpha, beta and gama). Once the receptor is activated the G protein is activated. The G protein is in the intracellular matrix - therefore when a GPCR is activated it also acts as an intracellular messenger that modules ion channels.

= GPCR are not just ion channels they are also biochemical pathways.

They can either excite or inhibit post-synaptic cells.

Question 41

What is vGLUT?

Answer 41

Vesicular glutamate transporter

Question 42

What is EAAT?

Answer 42

Excitatory amino acid transporter (e.g., gluatmate)

Question 43

What are the features of neuropeptides?

Answer 43

Small proteins

They are stored in large granular vesicles (LGV) which may contain other neurotransmitters.

They only act on G-Protein couples receptors.

They modulate synaptic transmission (strengthen or weaken synapse interactions).

They can be slow acting and longer lasting.

Question 44

What is an example of a gas neurotransmitter?

Answer 44

Nitrix Oxide

Question 45

Explain the difference between a chemical and electrochemical gradient

Answer 45

A chemical gradient, or in other words a concentration gradient, is the energy provided by the difference in the concentration of certain ions across the membrane. This deviation in concentration creates a chemical gradient which acts as a driving force because everything wants to move from an area of high concentration to an area of low concentration. For example, due to potassium being in higher concentration inside the cell there is a chemical gradient that drives potassium ions to move outside the cell.

An electrochemical gradient considers both the chemical gradient (concentration difference) and the electrical gradient (membrane potential across a membrane). An electrical gradient is the energy associated with moving charged molecules across the membrane. Ions are charge particles, so their movement across the membrane is influenced not only by difference in concentration but also by the electrical potential across the membrane.

Working out the electrochemical gradient (by using the Nernst equation) is important for determining the direction an ion will want to move. Take potassium for example: there is a high concentration of potassium ions inside the cell (therefore a chemical driving force to move outside the cell) but the inside of the cell is negatively charged compared to the outside (therefore the electrical gradient would be that the positively charge ion would want to remain inside in cell) – these driving forces contradict each other hence why the equation is required.

Question 46

What is the Nernst Equation?

Answer 46

Equilibrium Potential of Singular Ion = 61/charge of the ion x log x (concentration outside / concentration inside)

Question 47

What is the basis of the resting membrane potential, and how it is maintained

Answer 47

Every cell has a resting membrane potential (RMP). The RMP is the electrical potential across the membrane of a cell when it is at rest, this is typically -70mV in neurons.

The RMP is maintained by a balancing act between the distribution of ions across the cell membrane, primarily sodium, potassium and chloride.

The membrane is selectively permeable meaning it allows certain ions to pass through more easily than others. At rest, potassium ions have a higher concentration inside the cell, whilst sodium and chloride have a higher concentration outside the cell. Ions move in the direction of high concentration to low concentration. Therefore, this result in a resting gradient which acts as a driving force moving potassium out of the cell and sodium and chloride into the cell. The membrane contains ion channels for this movement. The cells membrane permeability to sodium is much lower than potassium, so the membrane potential is primarily determined by the permeability to potassium ions.

The is also a sodium-potassium pump. This pump actively transports sodium ions out of the cell and potassium ions into the cell against their concentration gradients. It pumps three sodium ions for every two potassium ions, this contributes to the overall negative charge into the cell.

The combination of these movements results in a delicate balancing act that determines and maintains the RMP.

Question 48

Describe the key characteristics of a local potential

Answer 48

Local potentials are small changes in the membrane potentials as a result of ions crossing the membrane. They occur at the dendrites/cell bodies. They are graded in size, decrease in amplitude over distance, they summate in time and space, they can depolarize and hyperpolarize, and they can influence the generation of an action potential.

Question 49

Draw and label a diagram to explain the difference between hyperpolarization, depolarization, and repolarization of the cell membrane

Question 50

Draw and label a diagram to show the changes in Na+ and K+ movements through the membrane during the action potential

Answer 50

Should show that K+ has slower kinetics than voltage gated Na+ channels - hence K+ drives hyper polarisation.

Question 51

List the important properties of the Na+ and K+ channels that allow the action potential to occur

Answer 51

It is Na+ that drives depolarization and the opening of K+ channels that drive repolarization.
There is an inactivation gate on the Na+ channels which can be referred to as the ‘ball and chain’ model. When it is not active the pore is closed, and positive charge is in the way therefore Na+ is not flowing through channel. When there is a charge in the voltage due to a depolarization the gate is activated causing the pore to open (the positive charge move away but remains nearby for selectivity) and Na+ can freely move into the cell. The increase in Na+ drives depolarization but an AP will only be generated if this happens to enough channels so that threshold it reached. Once threshold has been reached and an action potential generated then the gate is inactivated which means that the pore is still open, but the ball has moved to block the end of the channel. This is known as the absolute refractory period. The ball will automatically move back out again so that channel is no longer blocked but will be not activated again until depolarization.

The voltage gated K+ channels are activated in the same way as a Na+ channel (by depolarization) but they have much slower kinetics. Hence, why they often open at the time the sodium channels close and it is K+ channels that drives hyperpolarization.

Question 52

Describe the ionic and molecular basis for the two types of refractory period exhibited by action potentials in axons

Answer 52

The two types of refractory periods are the absolute refractory period (impossible for another AP to be generated) and the relative refractory period (very unlikely and rare for an AP to be generated).

Question 53

Describe the axonal adaptations that increase action potential conduction velocity and explain how they do so

Answer 53

Speed of conduction of an AP is determined by the axon diameter and myelination of the axon.

A large axon diameter increases speed because there is more capacity and less resistance. Myelination increases speed because it increases axon insultation which reduces current leak. Myelination also increases speed by its production of Nodes of Ranvier where there is a high density of Na+ channels. Due to the high density of channels, there is an instantaneous transfer of depolarization jumping from node to node which is faster. This is called saltatory conduction.

Question 54

Briefly describe the difference between electrical and chemical synapses

Answer 54

Chemical synapses are slower than electrical synapses which are very fast. Chemical synapses relies on neurotransmitters crossing the gap which are previously packaged in vesicles (there is a complex series of events for this to happen), whereas in electrical synapses ion flow directly from cell to cell which are connected by gap junctions.

Whilst electrical synapses are faster they lack the flexibility and modulation seen in chemical synapses.

Question 55

Use a diagram to explain the key features and timing of events at a chemical synapse

Question 56

Describe and explain the different types of synaptic (local potential) summation and modulation

Answer 56

Temporal Summation refers to time. Temporal summation occurs when two changes in membrane potential reach the axon hillock at the same or very similar time such that they summate together.

Spatial Summation refers to space but is also dependent on time. Spatial summation occurs when two EPSPs are initiated on two different dendrites arrive at the axon hillock at the same time because they are at the same distance from the axon hillock.

Question 57

Describe the classification of the types of neurotransmitters, and give examples of each

Answer 57

The three types of neurotransmitters we are concerned with are small molecules, peptides, and gases.

Small molecules are class neurotransmitters which are stored in vesicles that fuse with membrane. These neurotransmitters act on ionotropic and G protein coupled receptors. An example of a classic small molecule neurotransmitter is glutamate.

Peptides are short chains of amino acids linked by peptide bonds. Examples of neuropeptides are hypothalamic hormones.

An example of a gas neurotransmitter is nitric oxide.

Question 58

Describe the classification of the types of neurotransmitter receptor

Answer 58

Neurotransmitter receptors are classified based on their structure, function and the type of response they produce upon neurotransmitters binding. There are two main classes of neurotransmitter receptors: ionotropic receptors (ligand-gated ion channels) and metabotropic receptors (GPCR).

Ionotropic Receptors are membrane proteins that form ion channels. G Protein-Coupled Receptors are also membrane proteins but do not form ion channels themselves. Instead, when a neurotransmitter binds to the receptor it activate an associated G-protein and its subunits which initiates a signaling cascade inside the cell which can lead to various cellular responses.

Metabotropic receptors mediate slower but longer lasting responses than ionotropic receptors.

Question 59

Describe the glutamate transport cycle

Answer 59

The glutamate transport cycle is a process involved in the reuptake of the neurotransmitter glutamate from the synaptic cleft back into presynaptic terminals or surrounding glial cells.

Glutamate is stored in synaptic vesicles of nerve terminals until it is released by exocytosis into the synaptic cleft.

After glutamate fulfills its role in neurotransmission, it is rapidly cleared from the synaptic cleft by EAAT’s (excitatory amino acid transporters) to prevent excessive stimulation of the postsynaptic neuron. EAAT’s are located on surrounding astrocytes and, to a lesser extent, on neurons. The major transporters involved are EAAT1 and EAAT2 on astrocytes and EAAT3 on neurons.

Once inside the astrocytes, glutamate is converted into glutamine (non-neuroactive) by the enzyme glutamine synthetase.

Glutamine is then transported out of the astrocytes and into the extracellular space, where it can be taken up by neurons via specific glutamine transporters.

Within the neurons, glutamine is converted back into glutamate by the enzyme glutaminase. This newly synthesized glutamate is then packaged into synaptic vesicles by vesicular glutamate transporters (VGLUTs), ready to be released during the next synaptic transmission.

Question 60

Understand how excitatory and inhibitory synapses elicit responses in the post synaptic cell

Answer 60

Excitatory synapses depolarize the postsynaptic membrane, making it more likely to generate an action potential, while inhibitory synapses hyperpolarize the postsynaptic membrane, reducing the likelihood of action potential generation.

Glutamate is an excitatory neurotransmitter. When it is transported by EAAT’s sodium ions are co-transported activating post synaptic receptors and allowing more positively charge ions to enter the post synaptic neuron. The influx of Na+ ions depolarizes the post synaptic membrane bring it closer to threshold – it is a numbers game and if enough threshold will be reached and an AP generated.

Inhibitory synapses typically involve neurotransmitters such as GABA. They activate postsynaptic receptors that allow negatively charges ions to enter the post synaptic neurons or positively charged ions to leave the cell. The influx of negatively charged ions or the reduction of positively charged ions hyperpolarized the post synaptic membrane making it more negative and less likely to reach threshold for an AP.

Question 61

Where do local potentials occur?

Answer 61

Dentrites/cell bodies

Question 62

What does the Nerst potential tell us?

Answer 62

The membrane potential for a single ion

Question 63

What does the NaK-ATPase do?

Answer 63

Maintains RMP.

Uses energy from ATP to move K+ and Na+ against their concentration gradients. (Takes 3 Na+ ions out of the cell for every 2 K+ ions into the cell).

Which is done in balance with Na+ and K+ flowing across the membrane through ion channels down concentration gradient.

Question 64

Is the membrane more permeable to K+ or Na+?

Answer 64

K+

Membrane has more K+ channels than Na+ channels - therefore it is the concentration of K+ that primarily determines RMP.

Question 65

What is the composition of voltage-gated Na+ channel?

Answer 65

Two beta subunits and four alpha subunits.

Question 66

What are voltage gated K+ channels blocked by?

Answer 66

TEA - tetraethylammonium

Question 67

Approx how long does absolute refractory period last?

Answer 67

1-2ms

Question 68

Are gap junctions always open?

Answer 68

No - can be opened by voltage, pH, receptors and Ca2+

Question 69

Where are EPSP recorded?

Answer 69

Cell Bodie

Question 70

Where are EAAT’s located?

Answer 70

Gilal cells and post synaptic cell membrane.