Patient - Excitable Cells

Question 1

Describe how the heart works with regards to external control and external modulation

Answer 1

Does not require external control, contraction cycle is spontaneous, without external trigger. Cycle involves fine coordination of different parts of the heart.
Heart function is responsive to external modulation, however

Question 2

Give examples of external modulation of the heart

Answer 2

Autonomic nervous system, other hormones, physical factors

Question 3

Why is the cardiac function able to be spontaneous?

Answer 3

Cells store energy as a concentration difference of ions (inside/outside)
Membrane proteins control passage of ions, creating electrical activity and excitability
electrical signal can travel rapidly to neighbouring cells
electrical activity is coupled to mechanical action (contraction)

Question 4

Where are the specialised conducting cells in the heart

Answer 4

sinoartial node
atrioventricular node
Bundle of his 
Bundle branches
Purkinje fibres

Question 5

Describe the appearance of cardiac muscle on a cellular level

Answer 5

Short (100-200um)
Strong, branching cells held together at intercalated discs
Electrical (gap) junctions allow cell-to-cell spread of action potentials (in 3D) without chemical synpases

Question 6

What is the first stage of the cardiac cycle?

Answer 6

Sinoatrial node activity and atrial activation begins

Question 7

What happens after the atria activate with regards to excitability of cells?

Answer 7

Stimulus spreads across the atrial surfaces and reaches the AV (atrioventricular) node

Question 8

What happens after AV node activation?

Answer 8

There is a 100millisecond delay at the AV node. Atrial contraction then begins,

Question 9

Where does the impulse go after the atria have contracted?

Answer 9

The impulse travels along the interventricular septum within the AV bundle and the bundle branches to the Purkinje fibres and, via a moderator band, to the papillary muscles of the right ventricle

Question 10

What happens after the impulse has reached the papillary muscles of the right ventricle?

Answer 10

The impulse is distributed by the Purkinje fibres and relayed throughout the ventricular myocardium. Atrial contraction is completed, and ventricular contraction begins

Question 11

Summarise the route of cardiac action potentials generated and spread by the pacemaker/conducting system

Answer 11

1) Produced by SA node cells
2) Depolarise and contract atrial muscle cells
3) Atrial APs depolarise AV node
4) Spread along right and left bundle branches
5) Into Purkinje cell network to contact ventricles
6) Repeated to produce cardiac cycle

Question 12

Which cardiac conductive tissue is responsible for keeping atrial and ventricular systole separate?

Answer 12

The AV node as it delays the signal before it goes to the bundle of his

Question 13

What percentage of cardiac cells are specialised for contraction? i.e. regular muscle cells

Answer 13

~99%

Question 14

What percentage of cardiac cells are pacemaker and “specialised conducting” cells?

Answer 14

~1%

Question 15

typical Na+ in mM:

Extracellular and intracellular

Answer 15

extracellular: 145mM
intracellular: 14mM

Question 16

typical amount of K+ in mM

Extracellular and intracellular

Answer 16

Extracellular: 4mM
Intracellular: 140mM

Question 17

Typical amount of Ca2+ in mM

extracellular and intracellular

Answer 17

extracellular: 2mM
intracellular: <0.001mM

Question 18

Describe the plasma membrane in 3 statements

Answer 18

Bilayer of phospholipids.
Proteins inserted into the bilayer.
Proteins associated with bilayer surface.

Question 19

Is the lipid bilayer an electrical insulator or an electrical conductor? What does this mean?

Answer 19

Electrical insulator - stops stuff going past i.e. segregate charged particles
Barrier to passage of most molecules

Question 20

Does the lipid bilayer allow water flow?

Answer 20

Yes

Question 21

What is the lipid bilayer permeable to?

Answer 21

Small lipophilic (nonpolar) molecules

Question 22

2 kinds of ion channel

Answer 22

Ion selective

Gated

Question 23

4 kinds of gated ion channel

Answer 23

• Ligand gated (fast) receptor and gate in the same unit
• Second-messenger, enzyme linked, such as GPCR
• Voltage-gated, sensitive to transmembrane electrical potential
• Mechanical (stretch) gated

Question 24

What creates the transmembrane electrical potential?

Answer 24

Selective permeability to charged solutes

Question 25

Define Nernst (equilibrium) potential

Answer 25

The electrical potential that balances the chemical potential (so no net movement of ions)

Question 26

give the nerst (equilibrium) potential equation

Answer 26

Vm= (60mV/z) x log ([X]out/{X}in)
Where Vm= voltage inside relative to outside, units of millivolt
[X} is the concentration of X
z is the charge of ion X (e.g. -1, +2 etc)

Question 27

How to calculate the Vm (voltage inside relative to outside) when there are multiple penetrating solutes? which equation?

Answer 27

Goldman-Hodgkin-Katz (GHK) equation

Contribution of membrane potential is weighted according to permeability

Question 28

Van’t Hoff equation states what?

Answer 28

Chemical energy is proportional to solute concentration

Question 29

What is the implication of the 3 equations below combined?
Van’t Hoff equation
Nernst equation
Goldman/GHK equation

Answer 29

Gated ion channels can rapidly change the membrane voltage, without any change in bulk intracelluar concentrations, on a time scale as fast as ~1ms (nerve action potential)

Question 30

What is the cause of differences in action potential shapes?

Answer 30

Different gated cation channels

Question 31

Describe the pacemaker potential in a nodal cell

Answer 31

Cation permeabilities vary over time, affected by autonomic nervous system inpit

Question 32

What is the action potential upstroke in a nodal cell graph due to?

Answer 32

Due to voltage-gated Ca2+ channels

Question 33

What is the action potential downstroke due to?

in nodal cells

Answer 33

Increase in concentration of K+

Question 34

What are the currents in nodal cells activated by?

Answer 34

sympathetic stimulation (AdRs, e.g. noradrenaline) 
which open Na+ and Ca2+ channels and increase their concentration

Question 35

In pacemaker cells, describe how spontaneous slow depolarisation occurs

Answer 35

Na+ (and K+)

Transient Ca2+ channels

Question 36

In pacemakers cells, describe how rapid depolarisation occurs

Answer 36

due to slow Ca2+ channels

Question 37

How does repolarisation in pacemaker cells occur

Answer 37

K+ channels

Question 38

Describe atrial and ventricular contractile muscle contractile cells action potential

Answer 38

1) Resting membrane potential
2) Depolarisation
3) Slight repolarisation
4) Plateau to maintain contraction
5) Repolarisation (further)
6) Resting membrane potential

Question 39

Describe which channels open and close and relative concentrations at the following moments with a star on

1) Resting membrane potential
2) Depolarisation*
3) Slight repolarisation*
4) Plateau to maintain contraction*
5) repolarisation (further)*

Answer 39

2) FAST Na+ channels open therefore influx of Na+
3) Na+ close therefore efflux of Na+
4) Open Slow Ca2+ channels and close Ka+ therefore influx in Ca2+ and decrease of intracellular K+
5) slow Ca2+ channels close therefore efflux of Ca2+ and opening of K+ channels

Question 40

Resting membrane potential of a contractile cardiac cell

Answer 40

-90mV

Question 41

What is the depolarised membrane potential of a contractile cardiac cell when it is at plateau stage and the membrane depolarisation is extended?
How long does this last?

Answer 41

~0mV for >100ms