Electrical properties of the heart

Question 1

The potassium hypothesis

Answer 1

• The membrane is more permeable to potassium ions than anything else and these can diffuse down a concentration gradient, carrying positive charge with them.
• As they move, the incident chamber becomes increasingly positive related to the other chamber (as other negative ions cannot move due to the barrier being impermeable to them).
• The electrical gradient then directly opposes the concentration gradient and eventually you get a point when the electrical gradient = the concentration gradient and equilibrium is achieved
• Here K+ ions randomly move back and forth

Question 2

What does the RMP depend on and how can the resting membrane potential be predicted?

Answer 2

The membrane potential depend on the flow of K+ out of cells.
Using the Nernst equation

Question 3

What happens if the membrane is only permeable to K+?

Answer 3

If the membrane is only permeable to K+ then then potential across it will equal the K+ equilibrium potential.
The value for this is -80mV very close to actual RMP

Question 4

What will cause the membrane’s potential to change?

Answer 4

The membrane’s potential will change depending on the relative permeability of the membrane to different ions

Question 5

What happens if the membrane is only permeable to Na+?

Answer 5

When the membrane is only permeable to Na then the membrane potential is equal to the Na equilibrium potential.

Question 6

What is a better equation to predict membrane potential over Nernst equation?

Answer 6

The membrane potential is better describe by the Goldman Hodgkin Katz equation which takes into account relative permeabilities of ions

Question 7

What is the duration of a cardiac action potential and why?

Answer 7

• Cardiac action potentials last between 200 and 400ms (long)
• The duration of the AP controls the duration of contraction of the heart
• > long, slow contraction is required to produce an effective pump

Question 8

At rest what is membrane potential mainly determined by and why?

Answer 8

• At rest, membrane potential determined by K+
• Large membrane permeability to K+ stabilises membrane potential reducing risk to arrhythmias by requiring a large stimulus to excite the cells

Question 9

Cardiac action potential sequence

Answer 9

1. AP causes large change in PNa causing rapid upstroke
2. Large [Na+] Intracellular inactivates Na channels and thus reduces PNa quickly and this causes a brief increase in PK which gives the characteristic notch on the graph as K leaves the cell. Na channels enter absolute refractory period.
3. Large [Na+] intracellular also increases PCa early in plateau via LTCC. Influx provides trigger for Ca2+ release from intracellular stores for contraction.
4. The Ca2+ intracellular increase combined with the K+ efflux maintains the plateau of the graph.
5. Plateau ends when PCa decreases and a slow and small increase in PK occurs.
6. Repolarisation occurs due to inactivation of LTCC and opening of another subtype of K+ channels.

Question 10

What is absolute, relative refractory period?

Answer 10

Absolute - time during which no action potential can be initiated

Relative- period after ARP when and AP can be initiated but it must be larger than normal

Question 11

What causes refractory periods?

Answer 11

Sodium channel inactivation which reactivate at repolarisation

Question 12

What do long ARPs and RRPs prevent?

Answer 12

tetany

Question 13

What is full recovery time?

Answer 13

The time at which a normal AP can be elicited with a normal AP.

Question 14

Skeletal muscle vs cardiac muscle re stimulation and tetanising

Answer 14

In skeletal muscle repolarisation occurs quickly so restimulation and summation is possible

In cardiac muscle you cannot re excite the muscle until contraction is well underway to prevent tetanising the cardiac muscle

Question 15

What are the phases of the AP?

Answer 15

phase 4- resting membrane potential
phase 0- upstroke
phase 1- early repolarisation
phase 2 -plateau
phase 3 - repolarisation

Question 16

What are the intrinsic properties of the heart?

Answer 16

• The heart has its own independent electrical impulse generation and propagation system.
• The nature of the heart means even if disconnected with it’s supplying nerves; it can still beat.
• The internal electrical activity is modulated by sympathetic and parasympathetic nerves.

Question 17

What happens during phase 1?

Answer 17

Inactivation of sodium channels (no further depolarisation) and the transient outward potassium current starting.

Question 18

What happens during phase 2?

Answer 18

• Large intracellular sodium causes calcium influx which triggers CICR from intracellular stores.
• Potassium efflux and calcium influx stabilise the membrane potential around 0mV.
• Calcium influx can be blocked by dihydropyridine calcium channel antagonists (bind to LTCC, blocking the channel) such as Nifedipine, Nitrendipine and Nisoldipine.

Question 19

What can Nifedipine, Nitrendipine and Nisoldipine do?

Answer 19

They are dihydropyridine calcium channel antagonists which can bind to LTCC and block the channel preventing calcium influx.

Question 20

What happens in phase 3?

Answer 20

• Small potassium current starts to activate towards the end of the plateau which begins repolarisation.
• As the membrane becomes repolarised (due to efflux of potassium via normal potassium channels), the IK1 potassium channel switches back on (it turns off during depolarisation).
• The IK1 current is large and flows during diastole -> it acts to stabilise the resting membrane potential and reduce risk of arrhythmia.

Question 21

Different action potential profiles in the heart

Answer 21

• Different parts of the heart have different action potential shapes due to different ionic currents flowing due to expression of different ionic channels.
• These graph shapes combined create the iconic PQRST shaped wave.

Question 22

What happens in phase 4 and 0?

Answer 22

• Resting membrane potential is determined by K+ moving out of cells
• Upstroke is determined by a large increase in membrane permeability to sodium

Question 23

Which channels are present in the SA node and why?

Answer 23

• Most of the types of channels exist in the SA node cells with the exception of IK1.
• The function of IK1 is to maintain a stable membrane potential so SA node cells do not have a stable membrane potential.
• There is very little sodium influx into SA node cells, instead, the upstroke is caused by Ca2+ influx.
• The SA node cells contain T-type Ca2+ Channels (TTCC) which activate at a more negative potential than LTCC.
• The ITO (transient outward) current is very small.
• The pacemaker current If is present.

Question 24

How does the pacemaker potential affect heart rate?

Answer 24

• With sympathetic stimulation of the heart (e.g. adrenaline), it makes the pacemaker potential (the gradual upward slope before the -40mV line) steeper
• This means threshold potential is reached more quickly
• With parasympathetic stimulation (e.g. ACh) there is a decrease in the gradient of pacemaker potential
• Takes longer for membrane potential to meet the threshold thus reducing heart rate.
• This is how autonomic nervous system modulates heart rate.

Question 25

What are the four parts of the cardiac conduction system?

Answer 25

• Sinoatrial Node (Located in the right atrium)
• Inter-nodal Fibre Bundles
  (Conduct AP to AV-node at a greater velocity than ordinary atrial muscle?)

Atrioventricular Node
(Produces a delay of ~100ms)

Ventricular Bundles (bundle branches, purkinje fibres).
Bundle of His descends from AV-node and splits into two bundle branches made of Purkinje fibres 
Purkinje Fibres - conduct AP at around 6x the velocity ordinary cardiac muscle and penetrate 1/3rd distance into myocardial wall.

Question 26

How are impulses propagated between cells?

Answer 26

By using gap junctions which cluster at intercalated discs and have low resistance

Question 27

The basics of an ECG

Answer 27

• When a wave of depolarisation moves towards the positive electrode, an upward deflection is detected.
• When a wave is moving away from the positive electrode, a downward deflection is detected.
• Repolarising waves have the opposite effect on the trace.

Question 28

How is the intrinsic heart rate modulated?

Answer 28

Increased parasympathetic stimulation of SA node decreases heart rate and increases sympathetic stimulation increases heart rate and strength of contraction. Vagus nerve and sympathetic nerves involved as well and cardioregulatory and vasomotor centres in medulla oblongata

Question 29

Where is the SA node located?

Answer 29

Lies just below the epicardial surface at the boundary between the right atrium and SVC.

Question 30

How are impulses propagated?

Answer 30

The propagation of the cardiac action potential is due to a combination of passive spread of current and the existence of a threshold. The spread of current excites neighbouring cells easily because the membrane resistance between cells is low due to gap junctions. Gap junction resistance determine the extent of current spread.

Question 31

Pathway of electrical conduction through the heart

Answer 31

SAN -> LA (via bachmann's bundle)
SAN -> AVN (via internodal branches)
AVN -> Bundle of His
BOH -> L and R bundle branch
L/R Bundle branch -> purkinje fibres

Question 32

What is the pacemaker potential?

Answer 32

The slow, positive increase in voltage across the cell’s membrane at the start of the AP

Question 33

AP sequence in the SAN

Answer 33

Permeability to sodium increases so shallow upward stroke, then permeability to calcium so rapid upstroke, inactivation of calcium channels and then potassium channels open causing a downward stroke and then potassium channels close

Question 34

What is a graded potential?

Answer 34

Change in amplitude, can be bi-directional
Found at synapse and sensory receptors - if leads to an AP then called a generator potential
They decrease in amplitude over time and distance as charge leaks

Question 35

What is the function of a graded potential?

Answer 35

To generate or prevent AP

Question 36

What are the features of an AP and what is it preceded by?

Answer 36

uniform - all or nothing principle

preceded by generator potential