Cellular and Molecular mechanisms the Heart and Vasculature

Question 1

hoe does K+ permeability set the RMP in cardiac myocytes

Answer 1

• cardiac myocytes are permeable to K+ ions at rest.
• K+ ions move out of the cell down the conc gradient which makes the inside negative with respect to the outside. As charge builds up an electrical gradient is established.

Question 2

how excitation leads to contraction in cardiac myocytes.

Answer 2

-cardiac myocytes are electrically active so can fire action potentials which cause a big depolarisation.
-As cardiac myocytes are electrically coupled to each other when 1 depolarises it spreads to the others also depolarising them and contract together in a coordinated way.
the action potential triggers increase in cytosolic [Ca2+] which is required to allow actin and myosin interaction

Question 3

explain the different phases of the ventricular action potential

Answer 3

1) opening of V-gated Na+ channels
2) transient outward k+ current
3) opening of v gated Ca2+ channels
4) Ca2+ channels inactivate. v-gated k+ channels open

Question 4

explain the SA node action potential

Answer 4

1) pacemaker potential I(f)- influx of Na +
2) opening of v gated Ca2+ channels
3) opening of v-gated k+ channels

Question 5

why is the SA node the pacemaker

Answer 5

• fastest to depolarise
• sets rhythm
• AP initiated here.

Question 6

what happens if action potentials fire too slowly in the heart

Answer 6

bradycardia

Question 7

what happens if action potentials fail in the heart

Answer 7

asystole-no contraction

Question 8

what happens if action potentials fire too quickly in the heart

Answer 8

tachycardia

Question 9

what happens if electrical activity in the heart is random

Answer 9

fibrillation

Question 10

why are cardiac myocytes so sensitive to changes in K+

Answer 10

K+ permeability dominates the resting membrane potential

heart has many different kinds of k+ channels

Question 11

effect of hyperkalemia in heart

Answer 11

Ek gets less negative so membrane potential depolarises a bit
this inactivates some voltage gated Na+ channels slowing down upstroke.

Question 12

risks with hyperkalaemia in heart

Answer 12

heart can stop

may initially get an increase in excitability

Question 13

treatment of hyperkalaemia

Answer 13

calcium glutinate

insulin+gluose - insulin will drive k+ into cells but you don’t want glucose levels to go down so you also give glucose.

Question 14

effects of hypokalaemia

Answer 14

k+ channels reduce their conductance prolonging duration of action potential
delays depolarisation

Question 15

what is the problem with hypokalaemia

Answer 15

longer action potentials can lead to early after depolarisations (EADs) which can lead to oscillations in membrane potential.
can result in ventricular fibrillation

Question 16

how does relaxation of cardiac myocytes occur

Answer 16

must return [Ca2+]I to resting levels
most is pumped back into SR (SERCA)- raised Ca2+ levels stimulates these pumps
some also exits across cell membrane

Question 17

how does excitation contraction coupling occur in smooth muscle

Answer 17

depolarisation can open V gated Ca2+ channels and Ca2+ can bind to CaM as there is no troponin in smooth muscle. the ca2+ CaM complex activates MLCK which phosphorylates regulatory light chain. myosin light chain must be phosphorylated to enable actin-myosin interaction.
another way : noradrenaline activates a1 receptors forming Gaq (G alpha q). sends IP3 as second messenger. SR has IP3 receptors that release Ca2+ which then follows the same pathway as before

Question 18

how is contraction of vasculature inhibited

Answer 18

• myosin light chain phosphatase dephosphorylates the myosin light chain
• MLCK itself can be phosphorylated by PKA inhibiting MLCK therefore inhibiting phosphorylation of myosin light chain and inhibits contraction

Question 19

differences between cardiac muscle and smooth muscle

Answer 19

• contraction of the heart is initiated by spread of APs from SA node.
• cardiac myocyte action potentials allows Ca2+. further Ca2+ is released from SR , increased intracellular Ca2+, Ca2+ binding to troponin C.
• contraction of vascular smooth muscle cells initiated by depolarisation or activation of a adrenoceptors. increased intracellular Ca2+, Ca2+ binding to calmodulin activating MLCK-phosphorylates myosin light chain