Session 4- Electrical and Molecular Mechanisms in the Heart and Vasculature

Question 1

what is the resting membrane potential of cardiac myocytes

Answer 1

-85mv

Question 2

what triggers action potentials in myocytes

Answer 2

increase in cytosolic (Ca2+)

Question 3

how long does the action potential last in a cardiac ventricle

sino atrial node

Answer 3

100ms

100ms

Question 4

cardiac action potential

Answer 4

• opening of V-gated Na+ channels
• transient outward K+ current
• opening of V-gated Ca2+ channels (some K+ channels also open)

Ca2+ channels inactivate and voltage gated K+ channels open

Question 5

what is threshold of cardiac action potential

Answer 5

+30mv

Question 6

sino atrial node action potential

Answer 6

• pacemaker potential influx of sodium ions
• slow depolarisation
• opening of V-gated Ca2+ channels
• opening of V-gated K+ channels

Question 7

features of the pacemaker potential

Answer 7

activated at membrane potentials that are more negative than -50mv

initial slope to threshold- I f funny current

the more negative, the more it activates

Question 8

what causes the upstroke/downstroke in the SA node action potential

Answer 8

opening of voltage gated Ca2+ channels

down stroke- opening of voltage gates K+ channels

Question 9

why are cardiac myocytes so sensitive to changes in potassium ions

Answer 9

k+ permeability dominates the resting membrane potential

Question 10

what is hyperkalaemia

Answer 10

plasma K+ concentration is too high >5.5mmolm.L ^-1

Question 11

what is hypokalaemia

Answer 11

plasma K+ concentration is too low >3.5 mmol.L^-1

Question 12

effects of hyperkalaemia

Answer 12

Ek gets less negative so the membrane potential depolarises a bit

this inactivates some of the voltage gates Na+ channels

• slows upstroke
• shorter AP - more rapid repolarisation

hyperkalaemia depolarises the myocytes and slows down the upstroke of the action potential

Question 13

risks with hyperkalaemia

Answer 13

the heart can stop- asystole
may initially get an increase in excitability
depends on extent and how quickly it develops

Question 14

how do you treat hyperkalaemia

Answer 14

calcium gluconate- reduce excitability

insulin and glucose- promotes movement of sodium ions in cell

these wont work if heart has already stopped

Question 15

effects of hypokalaemia

Answer 15

lengthens action potential

delays repolarisation

Question 16

problems of hypokalaemia

Answer 16

longer action potential can lead to early after depolarisation
this can lead to oscillations in membrane potential
can result in ventricular fibrillation
mechanism due to the way the K+ channels behave

Question 17

how does cardiac muscle contraction occur

Answer 17

• depolarisation open L-type Ca2+ channels in T-tubule system
• localised Ca2+ entry opens Calcium-induced calcium release channels in SR
• close link between L-type channels and Ca2+ release channels
• 25% enters across sarcolemma, 75% released from SR

Question 18

relaxation of cardiac myocytes

Answer 18

must return [ca2+] to resting levels

most is pumped back into SR
-raised Ca2+ stimulates the pumps

some exits across cell membrane

• sarcolemmal Ca2+ ATPase
• Na+/Ca2+ exchanger

Question 19

excitation contraction coupling at the vascular level

Answer 19

depolarisation opens VGCCs
4 calcium ions bind to calmoldulin
MLCK binds to calmodulin
MLCK + calmodulin phosphorylates myosin head

at the same time noradrenaline activates alpha 1 receptors stimulating calcium release
G alpha q causes the formation of DAG and IP3
DAG activates protein kinase C which inhibits MLCP
MLCP dephosphorylates myosin head which would inactivate it PKC prevents this

IP3 causes the release of calcium from the sarcoplasmic reticulim

Question 20

what enables the actin-myosin interaction

Answer 20

myosin light chain must be phosphorylated