Excitable tissues: neurons

Question 1

what are neurons?

Answer 1

Neurons (or nerve cells): the principal buildings blocks

and instruments of communication in the brain

Question 2

what are the two indications for direction of flow of electrical singals?

Answer 2

synaptic potentials

action potentials

Question 3

how do neurons communicate?

Answer 3

electrical signals (dendrites, cell body, axon)

chemical signals
synapses

Question 4

What is the resting membrane potential (RMP)

Answer 4

In neurons and their processes, the cytoplasm has a potential that is 50 to 70 mV lower (ie. more negative) than the potential
of the extracellular space.

Question 5

almost all cells in the body have a ___________

Answer 5

negatice resting membrane potential

Question 6

Why are neurons and muscle fibres excitable?

Answer 6

Because only neurons and muscle fibres can suddenly respond with a transient
change of this potential (ie. with an action potential) in response to a stimulus

Question 7

How are the intracellular potentials measured today?

Answer 7

The microelectrode recording technique

The patch-clamp technique

Question 8

There is more ____________ inside the cell in comparison to the extracellular fluid.

Answer 8

There is more negative charges inside the cell in comparison to the extracellular fluid.

Question 9

The RMP is due to…?

Answer 9

a) Unequal concentrations of Na+ and K+ inside and outside the cell
b) Unequal permeability of the cell membrane to these ions
[c) Electrogenic action of the Na-K pump – only a small contribution ! ]

Question 10

what are the two main types of ion channels (which have selective permeability to ions) in neurons?

Answer 10

a) Non-gated (‘leak’) channels
b) Gated channels (voltage-gated, ligand-gated*, or mechanically-gated)
- open at rest
- closed at rest

Question 11

In cell membrane of neurons, there are

many ______ channels, but very few _______channels.

Answer 11

In cell membrane of neurons, there are
many leak K+ channels, but very few leak Na+ channels.
At rest: PK+ / PNa+ ≈ 40 / 1

Question 12

How does unequal concentration and unequal cell membrane permeability to Na+ and K+ result in the negative RMP?

Answer 12

The concept of the ‘Equilibrium potential’:

Question 13

What is the concept of the equilibrium potential?

Answer 13

An intracellular potential at which the net flow of ions is zero, in spite of a concentration gradient and permeability.

Question 14

How is the equilibrium potential calculated for each ion?

Answer 14

Nernst equation

Question 15

What is rule #1?

Answer 15

The higher the permeability of the cell membrane to a

particular ion, the greater the ability of this ion to shift the RMP towards its equilibrium potential.

Question 16

What happens in the neuron’s membrane permeability at rest? Thus?

Answer 16

At rest, in neurons the membrane permeability is much higher to K+ than to Na+; therefore the RMP is closer to the equilibrium potential for K+ ( than the equilibrium potential for Na+ E ( K) ENa).

Thus, in comparison to glia cells, in neurons the RMP is less negative
than EK (about - 65 mV). This is due to a small contribution of the leak
Na+ channels !

Question 17

What is the goldman equation?

Answer 17

A way of calculating the value of the RMP taking into account both the concentration gradients and the relative permeability of the resting cell membrane to K+ and Na+ ions.

Question 18

Why is the potential inside neurons not constant?

Answer 18

Because it changes when ion concentrations change, or when membrane permeability changes!

Question 19

What is hyperpolarisation? (2)

Answer 19

If the potential becomes more negative
(eg. changes from -70 to -75 mV)

The potential inside the
cell moves closer to EK, and away from ENa

Question 20

what is depolarisation?

Answer 20

If the potential becomes less negative (eg.
changes from -70 to -60 mV)

The potential inside the cell moves away from EK and closer to ENa

Question 21

What is the action potential?

Answer 21

A brief fluctuation in membrane potential caused by a transient opening of voltage-gated ion channels, which spreads, like a wave, along axon.

Question 22

How does action potential occur?

Answer 22

Action potentials occurs after the membrane potential reaches certain voltage called the threshold (~ -55 mV).

Question 23

Why is the action potential significant? (2)

Answer 23

Information is coded in the frequency of action
potentials. Thus, APs can be regarded as a form of
‘language’ by which neurons communicate !
Action potentials occurs after the membrane potential reaches certain voltage called the threshold (~ -55 mV).

Action potentials are a key element of the process of signal transmission along (often very long !) axons.

Question 24

ionic mechanisms associated with each stage of AP: When MP reaches the threshold, there is a sudden
activation (opening) __________________

Answer 24

When MP reaches the threshold, there is a sudden activation (opening) of voltage-gated Na+ channels ( PNa+↑ )

Question 25

AP ionic mechanisms: Opening of _________channels is only short lasting, as these channels ______________

Answer 25

Opening of voltage-gated | Na+ channels is only short lasting, as these channels quickly inactivate

Question 26

What happens when the voltage threshold is reached?

Answer 26

When the voltage threshold is reached, sodium channels open and Na+ ions move into the cell along both the concentration and electrical gradient.

Question 27

influx of Na+ slows down and then stops when? (2)

Answer 27

1) The inside potential becomes positive (moves towards ENa+ ) and thus attracts Na+ ions less. 2) Na+ channels inactivate.

Question 28

what is rule #2?

Answer 28

When the current generated by an outside source flows trough the cell membrane from outside to inside → hyperpolarisation (the MP becomes more negative); when it flows from inside to outside → depolarisation (the MP becomes less negative).

Question 29

How are APs generated ‘physiologically’ in | CNS neurons ? (3)

Answer 29

● APs are first generated in the axon initial segment (‘axon hillock’) which has lowest threshold, and thus serves as the ‘trigger zone’ for APs. Axon initial segment EPSPs ● Depolarisation to threshold is evoked by excitatory postsynaptic potentials (EPSPs), which spread mainly passively from dendrites. ● Once generated, APs are transmitted actively along the axon, away from the cell body.

Question 30

What are the two types of axons?

Answer 30

a) Unmyelinated axons: small diameter (~ 1 µm); transmission of APs slow, continuous b) Myelinated axons: larger diameter (5-10 µm); transmission of APs fast, ‘saltatory’ (in large steps)

Question 31

What are two stages of action potential transmission | (in both types of axons) ?

Answer 31

(1) Passive spread | (2) Generation of action potentials

Question 32

What is the 'passive' spread of current?

Answer 32

1. (Subthreshold) depolarisation at one region of the membrane 2. Passive current flow (inside and outside the axon) 3. Depolarization of adjacent parts of membrane (cf. Rule #2)

Question 33

How far does this deprolarisation spread?

Answer 33

Current can spread passively only over | a short distance

Question 34

what is the structure of neurons with myelinated axons

Answer 34

Myelin sheath formed: - by oligodendrocytes in the CNS -by schwann cells in the PNS

Question 35

oligodendrocites and Schwann cells are two types of_________?

Answer 35

gilia cells

Question 36

how does myelination increase speed of AP conduction?

Answer 36

Myelination increases speed of AP conduction by increasing the efficiency of passive spread, and the fact that APs do not need to be regenerated at every part of cell membrane.

Question 37

Where are APs generated?

Answer 37

APs are generated only at nodes of Ranvier (current flows passively between nodes).

Question 38

how are Aps generated in sensory neurons?

Answer 38

The concept of 'the receptor potential'

Question 39

what is the receptor potential?

Answer 39

● When a stimulus acts on receptors in sensory neurons (eg. a mechanical stimulus acting on muscle spindles), it does not immediately evoke APs. ● First it evokes a graded depolarisation, known as ‘the receptor potential’. ● The receptor potential spreads passively to more distally located ‘trigger zone’ where APs are generated. ● APs then spread along the axon (myelinated or unmyelinated) towards the CNS. ● Information about the strength of the stimulus is coded in the amplitude of the receptor potential and the frequency of APs (analog–to-digital converter !)

Question 40

How is a ‘message’ transmitted from one | neurone to another neurone (or to muscle fiber)? (2)

Answer 40

Synaptic transmission between neurons Synaptic transmission between a neuron (motoneuron) and a muscle fiber (Neuromuscular junction = ‘End plate’)

Question 41

What are the two main types of chemical synapses | in the CNS?

Answer 41

Excitatory synapses | Inhibitory synapses

Question 42

Excitatory synapses?

Answer 42

depolarisation of the postsynaptic membrane called | the Excitatory Postsynaptic Potential ( EPSP )

Question 43

Inhibitory synapses

Answer 43

hyperpolarisation of the postsynaptic membrane | called the Inhibitory Postsynaptic Potential (IPSP )

Question 44

what are the excitatory synapses | Neurotransmitters?

Answer 44

mainly glutamic acid | (glutamate) or ACh

Question 45

what are the Inhibitory synapses | Neurotransmitters?

Answer 45

``` mainly GABA (gamma-aminobutyric acid) or glycine ```

Question 46

Ionic mechanism of EPSPs?

Answer 46

transient opening of channels permeable to Na +, K + and sometimes Ca2+

Question 47

Ionic mechanism of IPSPs?

Answer 47

usually transient opening of K + channels

Question 48

What are the classification of neurotransmitters?

Answer 48

1. Small molecule neurotransmitters (‘Classical’ neurotransmitters) 2. Neuropeptides (‘Neuromodulators’)

Question 49

what are small molecule neurotransmitters features? (4)

Answer 49

Usually fast action (within milliseconds), and direct on postsynaptic receptors - Amino acids: glutamate, GABA, glycine - Acetylcholine (ACh) - Amines: serotonin (5-HT), noradrenaline, dopamine

Question 50

What are Neuropeptides features? (3)

Answer 50

Large molecule chemicals that have an indirect ( ‘metabotropic’) action on postsynaptic receptors, or modulatory action on the effects of other neurotransmitters Slow (seconds to minutes) and usually more diffuse action Several dozens of neuropeptides have been identified which may be involved in communication between neurons

Question 51

what are the three factors that determine the synaptic factor?

Answer 51

The type of neurotransmitter / neuromodulator The type of neurotransmitter receptor/ channel complex expressed in the postsynaptic membrane The amount of neurotransmitter receptor present in the postsynaptic membrane – ’Synaptic plasticity’: LTP or LTD (*)

Question 52

Neurotransmitter inactivation (and recovery)? (4)

Answer 52

Diffusion away from the synapse Enzymatic degradation in the synaptic cleft (eg. Acetylcholine esterase degrades ACh ) Re-uptake (for most of the amino acids and amines) and recycling ! Involvement of specific neurotransmitter transporters in the presynaptic membrane;

Question 53

Integration of synaptic inputs by neurons

Answer 53

Each neuron receives thousands (!) of synapses; some excitatory, some inhibitory Each individual synapse, when activated, produces only very small (only ≈ 0.1 mV) postsynaptic potentials at axon initial segment (Note: the decay of the potential when they are passively conducted from dendrites) In order to depolarise the initial segment to the threshold, EPSPs need to be enhanced !