9. Electrical And Moleculae Mechanisms In The Heart And Vasculature

Question 1

Describe how potassium sets the RMP in a cardiac myocyte?

Answer 1

Cardiac myocytes permeable to K+ ions at rest
K+ ions move out of cell down concentration gradient
Small movement of ions makes the inside negate with respect to the outside
Electrical gradient is established

Question 2

What is the RMP of ventricular myocytes?

Answer 2

-90 to -85 mV

Question 3

What is Ek?

Answer 3

-95mV

Question 4

What do action potentials trigger in cardiac myocytes?

Answer 4

Increase in cytosolic [Ca2+]

Question 5

Why is a rise in cytosolic [Ca2+] required?

Answer 5

To allow actin and myosin interactions 
Generates tension (contraction)

Question 6

How many action potentials are required for a contraction?

Answer 6

1

Question 7

How long are cardiac ventricle action potentials?

Answer 7

~280ms

Question 8

What are the stages of ventricular action potential?

Answer 8

Opening of V-gated Na+ channels (depolarisation)
Transient outward K+ current (rapid repolarisation)
Oepning of V-gated Ca2+ channels (some K+ channels also open) - long lasting
Ca2+ channels inactivate V-gated K+ channels open (repolarisation)

Question 9

Why do some K+ channels open when V-gated Ca2+ channels open?

Answer 9

To stop the membrane potential going too positive

Question 10

What happens in the first part of the SAN action potential?

Answer 10

Pacemaker potential If
Influx of Na+
Long slow depolarisation to threshold
Funny current - more hyperpolarised, more they open

Question 11

What happens in the second stage of the SAN action potential?

Answer 11

Opening of V-gated Ca2+ channels

Question 12

What is the final stage of the SAN action potential?

Answer 12

Opening of V-gated K+ channels

Question 13

What is the pacemaker potential?

Answer 13

Initial slope to threshold (funny current)
Activated at membrane potential more negative than -50mV
More negative, the more it activates
HCN channels allow influx of Na+ ions which depolarises the cells
Turning off of K+ current

Question 14

What are HCN channels?

Answer 14

Hyperpolarisation-activated, Cyclic Nucelotide-gated channels
Sensitive to changes in cAMP

Question 15

Which is the fastest action potential in the heart to depolarise?

Answer 15

SA node

Question 16

What is the role of the SA node?

Answer 16

Sets rhythm
Is the pacemaker
Other parts of the conducting system also have automaticity but are slower

Question 17

What happens if action potentials fire too slowly?

Answer 17

Bradycardia

Question 18

What happens if action potentials fail?

Answer 18

Asystole

Question 19

What happens if action potentials fire too quickly?

Answer 19

Tachycardia

Question 20

What happens if electrical activity becomes random?

Answer 20

Fibrillation

Question 21

What is the plasma K+ concentration range?

Answer 21

3.5-5.5 mmol/L

Question 22

Why are cardiac myocytes so sensitive to changes in [K+]?

Answer 22

K+ permeability dominates resting membrane potential

The heart has many different kinds of K+ channels

Question 23

What are the effects of hyperkalaemia?

Answer 23

Depolarises myocytes and slows down the upstroke of action potentials
If you raise plasma K+ then Ek gets less negative so the membrane potential depolarises a bit
This inactivates some of the voltage gated Na+ channels

Question 24

What are the risks with hyperkalaemia?

Answer 24

Heart can stop - asystole
May initially get an increase in excitability - depolarisation means closer to threshold
Depends on extent and how quickly it develops

Question 25

What is the treatment for hyperkalaemia?

Answer 25

Calcium gluconate - shields membrane, makes it less excitable
Insulin and glucose - drives potassium into cells
These won’t work if heart already stopped

Question 26

What are the effects of hypokalaemia?

Answer 26

Lengthens the action potential

Delays repolarisation - happens more slowly

Question 27

What are the problems with hypokalaemia?

Answer 27

Longer action potential can lead to early after depolarisations
Can lead to oscillations in membrane potential
Can result in ventricular fibrillation

Question 28

Describe excitation-contraction coupling

Answer 28

Depolarisation opens L-type Ca2+ channels in T-tubule system
Localised Ca2+ entry opens calcium-induced calcium release (CICR) channels in SR
Most calcium is released form SR
Ca2+ binds to troponin C
Conformational change shifts tropomysoin to reveal myosin binding site on actin filament

Question 29

What happens during relaxation of cardiac myocytes?

Answer 29

Return [Ca2+]i to resting levels
Most is pumped back into SR (SERCA)
Some exits across cell membrane

Question 30

Describe the excitation contraction coupling in smooth muscle cells

Answer 30

Voltage gated Ca2+ channels open after depolarisation
Ca2+ binds to calmodulin (4 molecules)
Activates myosin light chain kinase (MLCK)
Phosphorylates myosin head and activates it
Myosin light chain phosphorylase (MLCP) removes phosphate form myosin

Question 31

What is alternative method for Ca2+ to be released in smooth muscle cells?

Answer 31

Noradrenaline activates alpha 1 receptors with Gq protein in cell
Separates into IP3 and DAG
IP3 then acts on IP3 receptors on SR and causes Ca2+ release
DAG activates PKC which inhibits MLCP