cellular and molecular events in CVS

Question 1

what sets up the resting membrane potential in cardiac myocytes?

Answer 1

• Cardiac myocytes are permeable to K+ ions at rest
• K+ ions move out of the cell – down their concentration gradient
• Small movement of ions makes the inside negative with respect to the outside
• As charge builds up an electrical gradient is established

Question 2

what is the relationship between the equilibrium potential for K+ ions and RMP?

Answer 2

• Ek = equilibrium potential for K+ ions
• K+ moves out until Ek is reached
• Ek ≠ RMP

Question 3

what is the value of Ek and RMP?

Answer 3

Ek = -95mV
RMP = -80 to -90mV

Question 4

1. how long is an action potential in SAN?
2. what is the RMP in the SAN?

Answer 4

1. 100ms
2. -60mV (at this point HCN channels open)

Question 5

1. how long is the action potential in cardiac ventricle?
2. what is the RMP in cardiac ventricle?

Answer 5

1. 100ms
2. -90mV

Question 6

what happens in the ventricular (cardiac) action potential?

Answer 6

1. depolarisation = opening of V gated Na+ channels
2. small repolarisation = transient outward K+ current
3. plateau phase = opening of V-gate Ca2+ channels
4. repolarisation = Ca2+ channels inactivate and V-gate K+ channels open

Question 7

what happens in SAN action potential?

Answer 7

1. initial slope to threshold = funny current which is activated at membrane potential more negative than -50mV, HCN channels allow for influx of Na+
2. upstroke = influx of Ca2+ through transient (T-type) and L-type Ca2+ channels
3. repolarisation = opening of V-gated K+ channels

Question 8

1. what happens if action potential is too slow?
2. what happens if action potential fails to fire?
3. what happens if action potential is too fast?
4. what happens if action potential is random?

Answer 8

1. bradychardia
2. asystole
3. tachycardia
4. fibrilation

Question 9

what is normal plasma concentration levels?

Answer 9

3.5 - 5.5 mmol/L

Question 10

what is the effect of hyperkalaemia on myocytes?

Answer 10

lower concentration gradient
Ek = less negative so membrane potential depolarises a bit
inactivates some of voltage gated Na+ channels so slower upstroke
repolarisation is earlier and quicker

Question 11

what are the different severities of hyperkalaemia?

Answer 11

mild = 5.5-5.9 mmol/L
moderate = 6.0 - 6.4 mmol/L
severe = >6.5 mmol/L

Question 12

what is the treatment of hyperkalaemia?

Answer 12

calcium gluconate
insulin + glucose
(these wont work if heart has already stopped)

Question 13

what are the consequences of hyperkalaemia?

Answer 13

can causes asystole:
* the QRS complex continues to widen and eventually blends with the T wave
* this causes V fib and asystole

Question 14

what is the effect of hypokalaemia on myocytes?

Answer 14

greater concentration gradient
more K+ moves out of cell so membrane potential is more negative
plateau phase is longer so longer action potential
repolarisation is delayed and slower

Question 15

what are the consequences of hypokalaemia?

Answer 15

longer action potential increases risk of EAD (early after depolarisation)
leads to oscillations in membrane potential
increased excitability of cardiac myocytes because there is a delay in repolarisation of the myocyte, meaning that the heart rate increases
can cause V fib

Question 16

what controls tone of blood vessels?

Answer 16

contraction and relaxation of vascular smooth muscle cells (found in the tunica media)

Question 17

what regulates contraction in vascular smooth muscle?

Answer 17

1. noradrenaline binds to alpha 1 adrenoreceptors which activates the G-alpha-Q pathway
2. stimulates IP3 and DAG receptors
3. IP3 stimulates release of Ca2+ from sarcoplasmic reticulum
4. calcium binds to calmodulin which activates the myosin light chain kinase
5. myosin light chain kinase phosphorylates the myosin light chain to allow for interaction with actin
   (PKA can phosphorylate the MLCK which inhibits its action)