3 - Excitable Tissues

Question 1

What are excitable tissues? And what are the major types?

Answer 1

• Tissues that utilise electrical signals that travel along cells and can be readily transferred from cell to cell
• Neurones and Muscle (skeletal, cardiac and smooth)

Question 2

How do you record the membrane potential in a single cell?

Answer 2

Use a voltmeter with microelectrodes. Place one extracellularly and one intracellularly, then measure the potential difference

Question 3

What is resting membrane potential?

Answer 3

Membrane potential of an excitable cell at rest. Membrane is polarised

Question 4

Define polarised

Answer 4

2 sides are different charges

Question 5

What happens during depolarisation

Answer 5

Membrane potential decreases in magnitude from RMP (inside of the cell becomes less negative)

Question 6

What happens during repolarisation

Answer 6

• Restoration of the difference in charge
• MP increases in magnitude back towards RMP
• Inside of the cell becomes more negative

Question 7

What happens during hyperpolarisation?

Answer 7

• MP increases in magnitude from RMP
• Membrane is more polarised (more negative)

Question 8

What happens during hyperpolarisation?

Answer 8

• MP increases in magnitude from RMP
• Membrane is more polarised (more negative)

Question 9

What are graded potentials? And what are their key characteristics?

Answer 9

• Occur when an excitable tissue is subjected to an excitatory/inhibitory stimulus
• Small changes in MP (1-30mv)
• Transient (lasting 10’s of ms)
• Proportional to size of stimulus
• Produce local not global effects (only effects part around the stimulus, not the whole cell)

Question 10

Explain depolarising graded potentials

Answer 10

• Produced by an excitatory stimulus applied to the cell
• Causes a transient depolarisation of the membrane

Question 11

Describe hyperpolarising graded potentials

Answer 11

• Inhibitory stimulus applied to the cell
• Causes a transient increase in the membrane potential
• More negative than the RMP

Question 12

What are the general features of an action potential?

Answer 12

• Large, fast complex changes in MP by large excitatory stimulus
• Affects the whole cell (once initiated, travels over the whole cell)
• To get an AP, depolarising GP must be large enough to reach threshold (varies from cell to cell)

Question 13

Describe the phases of action potentials

Answer 13

1. **Depolarising phase: **period between threshold and the peak. Inside of the cell is positive compared to the outside
2. Repolarising phase: Period between peak and RMP
3. Hyperpolarising phase: Becomes more negative before returning to RMP

Question 14

What are the typical membrane values at threshold and peak of action potential?

Answer 14

• Threshold: -65mV
• Peak: +30mV

Question 15

Key differences between graded and action potentials

Answer 15

1. AP always the same size, unlike GP (all or none principle. if threshold is reached, whole sequence occurs)
2. APs are quicker (AP = few ms)
3. Action potential propagation. Movement of AP. GP is localised.

Question 16

What is conduction velocity?

Answer 16

• Speed of AP propagation is rapid
• Vary b/n cells (0.5-130 m/sec)

Question 17

What is frequency encoding?

Answer 17

• APs encode info by frequency of APs
• Expressed in Hz
• Freq in excitable tissues = no. AP per second

Question 18

Describe an experiment for frequency coding

Answer 18

• Measuring MP of a neurone in response to skin indentation by blunt probe
• As the probe is advanced, series of AP in neurone that last as long as skin deformation and have a consistent frequency
• Increase the force applied to the probe, higher freq of AP happens
• Therefore, higher stimulus intensity is encoded by a higher freq of AP

Question 19

What are the normal intracellular and extracellular ion concentrations for major anions and cations in mammals

Answer 19

Question 20

What is the functional significance of ion selective channels, resting channels and gated ion channels?

Answer 20

Bc ions are dissolved in aqueous ECF and ICF, can’t move through hydrophobic core of lipid bilayer so they move through these channels instead.

Question 21

Explain voltage-gated ion channels and an example

Answer 21

• State of the gate is determined by MP
• Has a molecular sensor that measures MP
• Opens/closes depending on value
• E.g: VGNa+ and K+ channels in AP

Question 22

Explain ligand-gated ion channels and an example

Answer 22

• Gated by binding of chemicals to a receptor closely associated with the channel
• Interaction between ligand/chemical and receptor enables high specificity in controlling ion channel opening
• E.g: acute sense of smell
• Important in a wide variety of physiological systems and are implicated in a number of diseases and actions of therapeutic drugs

Question 23

Explain stretch-gated ion channels and an example

Answer 23

• Regulated by degree of stretch (mechanical deformation) exerted on membrane where they’re embedded
• Stetch produces a conformational shape change, opens the gate so ions pass
• Involved in initiating GP associated with sensory stimuli

Question 24

Explain resting channels

Answer 24

• Ungated
• Open most of the time, not affected by stimuli
• Important for RMP

Question 25

Describe the ionic-basis of the RMP

Answer 25

• At rest, membrane is freely permeable to K+ due to resting channels
• Higher concentration of K+ inside the cell and lower conc outside.
• K+ flows out of the cell down the concentration gradient

Question 26

Explain why the resting membrane potential is slightly less negative than the equilibrium potential for K+

Answer 26

• Membrane is slightly leaky, so some Na+ passes through
• Making it slightly less negative

Question 27

Ionic basis of action potential at threshold

Answer 27

• [Na] out > [Na] in. Therefore Na+ goes into the cell down conc gradient
• Inside of cell is negative, so EG attracts Na+ into the cell
• VGNa+ channels are closed at RMP, but are programmed to open during threshold.
• At threshold, membrane has increased permeability to Na+, so Na rushes into cell along CG and EG
• Membrane depolarises, as positive charge flows into cell. Inside of cell becomes less negative.
• Depolarisation causes more VGNaC to open and more Na goes into cell
• This positive feedback loop is responsible for the explosive nature of the depolarising phase of the action potential. Because the equilibrium potential for Na+ is around +56 mV, Na+ continues to flow into the cell even after the membrane potential reaches 0 mV and in fact continues on until it peaks at around +30 mV.

Question 28

Ionic basis of AP at peak

Answer 28

1. VGNaC close, some VGKC open
2. CG and EG favours movement of K+ out of cell
3. Net effect: influx of Na+ rapidly declines, more K+ leaving the cell along CG and EG
4. As a result of declining influx of positive charge (Na+) and an increase in efflux of positive charge (K+), AP peaks and rapidly repolarises
5. Repolarising phase is a direct consequence of K+ efflux

Question 29

Ionic basis of hyperpolarising phase

Answer 29

• Consequence of slow closing of VGK+C
• Those channels + resting K+ channels causes MP to be higher than RMP
• Slow closing of VGKC responsible for hyperpolarising phase

Question 30

Describe an experiment that could do to demonstrate that K+ is responsible for the resting membrane potential.

Answer 30

• Investigate the effects of varying conc of K+ in the solution bathing the cells on RMP
• Measure the RMP of 5 cells by placing a moveable electrode inside each of the cells in turn
• (In prac book)

Question 31

Describe an experimental approach that you could use to demonstrate that Na+ influx is responsible for the depolarising phase of the action potential.

Answer 31

Investigate the effects of varying extracellular [Na+] on the magnitude of the depolarising phase of the AP
(Prac book)

Question 32

Understand what the Goldman-Hodgkin-Katz equation is and how to use it to predict the membrane potential if you know the relative permeability of the membrane to K+ and Na+.

Answer 32

Question 33

Explain why the Goldman-Hodgkin-Katz equation provides a more accurate prediction of membrane potential that the Nernst equation.

Answer 33

Nernst eq assumes that channels are only permeable to 1 specific ion species. While this equation takes into account that channels may be permeable to more than 1 ion species.

Question 34

Explain why the Goldman-Hodgkin-Katz equation provides a more accurate prediction of membrane potential that the Nernst equation.

Answer 34

Nernst eq assumes that channels are only permeable to 1 specific ion species. While this equation takes into account that channels may be permeable to more than 1 ion species.

Question 35

Explain the mechanisms of action potentials

Answer 35

1. Initiation: AP initiated at axon initial segment (adjacent to axon hillock). This is because this part of the membrane has a lower threshold
2. Propagation: AP travels down the axon, away from the soma to the axon terminal.

Question 36

Explain how the mechanisms of action potential propagation differ between myelinated and unmyelinated axons and the implication that this has for conduction velocity.

Answer 36

Unmyelinated
* AP in membrane causes VGNaC to open in adjacent membrane
* Na+ goes into cell and initiates AP further along axon
* Conduction velocity is quite slow (0.5-2.5 m/s)
Myelinated
* Wrapped in thick myelin sheath
* Node of ranvier: gaps in myelin sheath, axon is exposed
* Heavy insulation from myelin enables VGNa+C to detect the voltage of AP in adjacent node (AP can jump from node to node)
* Called Saltatory conduction
* Therefore, slow propagation of AP along nodes, but very rapid saltatory communication between nodes
* Causes conduction velocity to be much quicker (12-130 m/sec)

Question 37

What are refactory periods?

Answer 37

• Refactory period keeps AP moving in 1 direction
• Region that AP has just passed through becomes refactory (inactive) for a short time
• Difficult to initiate AP in this part (hence 1 direction)

Question 38

Exaplin the ionic basis for absolute refactory periods

Answer 38

• When the second stimulus is applied, cell fails to produce AP
  Caused by:
• VGNaC hae opened then closed again
• They get “jammed”
• Called Na+ channel inactivation

Question 39

Explain the ionic basis of relative refactory period

Answer 39

• Small AP that gradually increases in size as the delay between stimuli increases
• AP with reduced amplitude
• Caused by gradual recovery of VGNaC
• As more and more of these Na+ channels come out of inactivation, more and more of them can be opened by the stimulus and more and more Na+ can flow into the cell. Because Na+ influx is responsible for the depolarising phase of the action potential the greater the influx of Na+ the bigger the action potential.