Session 4- heart contraction

Question 1

What does automaticity mean in the heart?

Which channels are responsible for automaticity?

Answer 1

Ability of nodal cells/ pacemaker cells to spontaneously depolarise and generate an action potential; thus setting the heart rate

HCN channels
(Hyperpolarisation-activated Cyclic Nucleotide-gated channels)

Question 2

How do the pacemaker cells depolarise?

Answer 2

• In diastole the membrane is repolarised (-60 mV). This potential activates the HCN channels
• Funny current flows into the cells and potential rises
• VOCC’s open which depolarises the cells (+30mV)
• VOCC’s close and voltage gated potassium channels open allowing K+ efflux from the cell
• Cell repolarises

Question 3

What causes the pacemaker cells to depolarise?

What potential do they rise to?

Answer 3

The resting membrane potential in diastole (-60 mV) activates the HCN channels which open to allow cation influx

+30 mV

Question 4

The action potential of pacemaker cells is mediated by which cation?

Answer 4

Calcium ions

Question 5

Why is the HCN mediated ion influx called, the ‘funny current’?

How does the funny current determine heart rate?

Answer 5

mix of Na+ and Ca+ ions

influx is very slow (poor kinetics) which means depolarisation is slow

Question 6

Why does the depolarisation rate of the SAN determine the heart rate when other cells have automaticity too?

Answer 6

bc the SAN rate is quickest and overrides others

Question 7

Cardiac myocytes depolarise from ____ mV to ____ mV?

Answer 7

-90 mV to + 30 mV

Question 8

Which channels mediate the early repolarisation phase of the cardiac action potential?

What is their current called?

Answer 8

Voltage gated potassium channels which open in response to depolarisation

Transient outward current (Ito)

Question 9

Which calcium channels are involved in the cardiac myocyte action potential?

Answer 9

T-type
L-type

T-type contribute to the rapid upstroke (phase 0) and (Transiently) open as the membrane potential rises

L-type channels open at a higher voltage and remain open longer. They allow a sustained calcium influx which creates the calcium plateau

Question 10

How many phases are there in the cardiac myocyte action potential?

Answer 10

4

Question 11

Which channels cause the rapid upstroke in cardiac myocyte depolarisation?

How are they activated?

When do they inactivate and what does this create?

Answer 11

Fast sodium channels

Activated by depolarisation of the membrane near the gap junction (adjacent cell)

Inactivate as potential rises (almost simultaneously with their activation)
- Creates the absolute refractory period- cannot generate another action potential bc no more Na+ ions can enter

Question 12

What generates the relative refractory period?

Answer 12

As membrane potential begins to fall, the fast Na+ channels (inactivated by high membrane potential) begin to recover
If the stimulus is large enough an action potential can be generated

Question 13

Which ion largely determines the RMP of the cardiac myocyte? Why?

Through which channels does the ion move?

Answer 13

Potassium ions
Myocytes are most permeable to K+ ions at rest

Kir channels (inwardly rectifying K+ channels)

Question 14

3 major actions of the Kir channels?

How?

Answer 14

• Generate RMP of ventricular myocytes
• Initiate depolarisation
• Initiate repolarisation
• Presence of Kir channels in the myocyte increases its permeability to K+ above permeability to any other ion at rest (Goldman Hodgkin Katz equation)
• K+ flows easily into the cell when the potential is repolarised (negative)
• When the cell is depolarised (positive) , K+ effluxes (via Kir) down its electric gradient

Question 15

What does ‘Kir channel’ stand for and how does it relate to their function?

Answer 15

inwardly rectifying potassium (K+) channel

channels favour inward movement of potassium ions

Question 16

What is the RMP of a cardiac myocyte?

Which ion determines the RMP and what is its equilibrium potential?

Answer 16

-90 mV

K+
-95 mV

Question 17

Normal potassium concentration?

Answer 17

3.5-5.5 mmol/ L

Question 18

What effect does hyperkalemia have on the cardiac myocyte?
Explain why

How can hyperkalemia become life threatening?

Answer 18

Makes it less excitable

Hyperkalemia raises the resting membrane potential because it’s proportional to the extracellular concentration of K+. This inactivates fast Na+ channels (inactivate at higher potentials) which slows the upstroke of depolarisation

If the heart can’t depolarises due to closed Na+ channels it cannot contract- asystole

Question 19

How do you treat hyperkalemia?

Answer 19

calcium gluconate / glucose and insulin

(insulin and K+ have the same transporter into the cell).

Question 20

What life threatening condition can hypokalemia cause?

Answer 20

ventricular fibrillation (no cardiac output)

Question 21

What’s the problem with extending the length of a ventricular action potential?

Answer 21

More likely for EAD’s to occur (early after depolarisations) which cause the membrane potential to oscillate and can cause arrythmias (VF)

Question 22

What effect does hypokalemia have on the ventricular action potential?

Why?

Answer 22

lengthens it

membrane repolarises slower because some potassium channels don’t work as well with low extracellular potassium

Question 23

ECG appearance in hyperkalemia?

ECG appearance in hypokalemia?

Answer 23

Peaked T waves
Small/ no p waves
Broad QRS
sine wave pattern if very high K+ levels

Low T waves
High U wave
Low ST segment

Question 24

Where is the U wave on an ECG?

What does it indicate?

Answer 24

after the T wave

delayed repolarisation
which causes EAD’s like the U wave
* early after depolarisations

Question 25

Which equation determines the equilibrium potential of an ion?

Which equation determines RMP of a cell?

Answer 25

Nernst
= RT/zF (Xo/Xi)

Goldman Hodgkin Katz
(sums the equilibrium potentials of all ions the cell is permeable to at rest)

Question 26

Which channels mediate calcium induced calcium release? (CiCr)

How are they activated?

In which muscle is CiCr important?

Answer 26

Ryanodine receptors on sarcoplasmic membrane

T tubule system transmits depolarisation deep into the muscle cell
L type calcium channels (VOCC) open
Trigger calcium induces RYR’s to open

cardiac muscle

Question 27

Which receptors on the SR require a substrate binding to open and release Ca2+?

Answer 27

InsP3R

inositol trisphosphate receptor

Question 28

Explain the sliding filament theory

What is rigor mortis? Why does it happen?

Answer 28

• Myosin head binds ATP; hydrolysis facilitates the head to assume cocked position and weakly binds actin
• Ca2+ binds Troponin C which induces a conformational change so Tropomyosin shifts to uncover the rest of the myosin binding site
• Mysoin releases the phosphate and completes power stroke
• Sarcomere shortens
• Myosin releases ADP and remains bound to actin until ATP attaches

Rigidity following death because the myosin heads can’t detach from actin as there’s no ATP

Question 29

What does Ca2+ bind to cause cardiac muscle contraction?

Answer 29

Troponin C

Question 30

Contraction in which muscle types is regulated by calcium binding to troponin?

What regulates contraction in the other muscle type?

Answer 30

skeletal
cardiac

smooth muscle is regulated by 4 Ca2+ binding calmodulin

Question 31

cAMP causes contraction in which muscle?

Relaxation in which muscle?

Answer 31

skeletal and cardiac

smooth muscle

Question 32

How does cAMP cause relaxation?

Answer 32

cAMP activates PKA (Protein kinase A) which inhibits MLCK

MLCK is necessary for smooth muscle contraction

Question 33

Why must MLC20 be phosphorylated in smooth muscle contraction?

Answer 33

Allows actin and myosin filaments to interact

Question 34

The cardiac action lasts how long at rest?

Answer 34

280ms