3.2 Cellular and molecular events in the heart

Question 1

What do the pacemaker cells of the heart have the intrinsic ability to do ?

Answer 1

spontaneously depolarise and trigger action potentials

Question 2

Action of pacemaker cells of the heart don’t require what ?

Answer 2

extrinsic input

Question 3

what do Non-contractile nodal cells intrinsically initiate ?

Answer 3

ion-dependent electrical events at regular intervals (60-80 per minute)

Question 4

..1… electrical impulses propagate from the ..2.., via the ..3… septum to the cardiac apex to initiate contraction of the ..4..

This spreads through the ..5.. to produce a co-ordinated heartbeat

Answer 4

1. Ion-dependent
2. SA node to the AV node
3. intraventricular
4. contractile cardiomyocytes
5. myocardium

Question 5

Cardiomyocyte contraction involves a force generated by what ?

Answer 5

a contractile apparatus where actin-myosin generates tension where intracellular calcium concentration rises.

this tension is proportional to intracellular calcium concentration

Question 6

What is the troponin complex ?

Answer 6

a component of the thin filaments in striated muscle complexed to actin

Question 7

what are the 3 types of troponins ?

Answer 7

• troponin T (tropomyosin binding)
• troponin I (inhibitory protein)
• troponin C (calcium binding )

Question 8

How do internal calcium concentration determine cardiomyocyte contraction / relaxation ?

Answer 8

intracellular calcium concentration must:
* rise to allow cardiomyocyte contraction during systole
* fall (to allow cardiomyocyte relaxation) during diastole

Question 9

How is intracellular calcium concentration elevated and then returned to basal levels ? [changes]

Answer 9

influx and efflux mechanisms of cardiac myocytes

Question 10

What do voltage-gated Ca2+ channels (VGCCs) of heart allow ?

Answer 10

An influx of Ca2+ into cells across the plasma membrane by opening in response to an increase in membrane potential (i.e. depolarisation)

Question 11

Where is Ca2+ released from in the heart ? [change!!]

Answer 11

rapidly-releasable intracellular stores

Question 12

what does the SERCA pump stand for?

Answer 12

sarco/endoplasmic reticulum Ca2+ ATPase

Question 13

what does CICR stand for ?

Answer 13

Ca2+ - induced Ca2+ release

Question 14

List the steps involved in the cardiac excitation-contraction coupling [change!!]

Answer 14

1. action potential enters from adjacent cell
2. voltage-gated Ca2+ channels open. Ca2+ enters cell
3. Ca2+ induces Ca2+ release through ryanodine receptor-channels (RyR)
4. Local release causes Ca2+ spark
5. summed Ca2+ sparks create a Ca2+ signal
6. Ca2+ ions bind to troponin to initiate contraction
7. relaxation occurs when Ca2+ unbinds from troponin
8. Ca2+ is pumped back into the sarcoplasmic reticulum for storage

Question 15

What does the elevated intracellular calcium concentration occur due to ?

Answer 15

an action potential in the cell membrane

Question 16

what is an action potential of the membrane potential of the cell ?

Answer 16

a characteristic disturbance

Question 17

1. What does it mean by cell membranes being ‘capacitors’?
2. what are membranes charged by ?
3. what are electrical current in biological systems carried by ?

Answer 17

1. they store electrical charge
2. movement of ions across them
3. ions not electrons

Question 18

When is an equilibrium established in the action potential of cardiomyocytes ?

Answer 18

at a membrane potential determined by the ratio of K+ concentrations inside and outside the cell

where the resting membrane potential of myocardial fibres is approximately -90mV

Question 19

What does it mean by each ion having an equilibrium potential ?

Answer 19

the hypothetical membrane potential that would develop if that ion were the only ion that could cross the membrane

Question 20

What are the equilibrium potentials of the following ?
1. K+
2. Na+
3. Cl-
4. Ca2+

Answer 20

1. -90mV
2. +50mV
3. -90 mV
4. +125mV

Question 21

What will happen to the membrane potential if the permeability of the membrane to different ions changes ?

Answer 21

it will change accordingly

Question 22

What channels do myocardial cell membranes have ?

Answer 22

• voltage-gated K channels
• voltage-gated Na channels
• voltage-gated Ca channels

Question 23

1. In diastole which ion is the cell membrane of myocardial cells mostly peremable to ?
2. so which ion equilibrium is the membrane potential close to ?

Answer 23

1. K+
2. K+ equilibrium potential

Question 24

1. What are ventricular cell stiumlated by ?
2. what does this do to the cell ?

Answer 24

1. spread of electrical activity from pacemaker cells
2. depolarises it = making less negative inside the cell

Question 25

What does the initial depolarisation of the cardiac action potential do ?

Answer 25

The depolarisation to a threshold opens ‘ fast’ voltage-gated sodium channels

So the membrane moves towards the sodium equilibrium potential (+50mV) and depolarises further

Question 26

why doesn’t the membrane potential repolarise quickly in cardiac myocytes when voltage gated sodium channels close ?

Answer 26

voltage-gated calcium channels open

Question 27

Why is there a plateau phase in the cardiac action potential ?

Answer 27

There is a lot more Ca2+ outside cells than inside cells so the Ca Equi Pot is +ve inside and the opening of calcium channels keeps the membrane depolarised

these channels stay open for 250ms so cell contraction is sustained for a long time but eventually close allowing membrane to repolarise

Question 28

What stimulates the calcium induced calcium release ?

Answer 28

open calcium channels allow calcium ions into the cell, which stiumlates release of calcium from the sarcoplasmic reticulum

resulting in Ca2+ allows actin-myosin interaction and cardiomyocyte contraction

Question 29

What happens at the same time that the Ca2+ channels close ?

Answer 29

extra potassium channels open making the cell repolarise faster

so calcium is sequestered within the cell, so intracellular calcium concentration falls, and the cell relaxes - diastole.

Question 30

Another name for pacemaker cells ?

Answer 30

non-contractile nodal cells

Question 31

Where are pacemaker cells found (1) and what can they generate (2) ?

Answer 31

1. in SA and AV node
2. action potentials spontaneously