Session 4: Cellular and Molecular Events in the Heart and Blood Vessels Flashcards

1
Q

Explain the ventricular (cardiac) action potential.

A

The cardiac action potential is longer than a nerve action potential.
It is usually at around -85 to -90 mV at resting membrane potential. There is the an opening of voltage gated sodium channels done by neighbouring cells which depolarise the cardiomyocyte quickly. As threshold is reached an action potential is propagated. There is then a quick attempt at repolarisation of a transient outward K+ current. However, and this is what is special for cardiomyocytes, there is an opening of voltage gated Ca2+ channels which with the K+ channels open as well makes the action potential balance at a plateau for a while. The calcium channel then inactivate and more voltage gated K+ channels open.

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2
Q

More briefly explain cardiac action potential.

A

Na+ influx = depolarisation
Ca2+ influx and K+ efflux = plateau
Ca2+ inactivation and K+ efflux = repolarisation

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3
Q

How is the resting membrane potential achieved?

A

By background K+ channels.

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4
Q

What type of voltage gated calcium channels are the ones that are opened at the plateau?

A

L-type

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5
Q

SA node action potential differs from cardiac action potential. How?

A

It can spontaneously depolarise and does not need a nerve impulse. There is an initial slope to the threshold which is called a funny current where there is an influx of Na+.
This influx is activated when the membrane potential becomes more negative than -50mV. This means that the depolarisation starts due to hyperpolarisation!
The channels are hyperpolarisation-activated cyclic nucleotide-gated channels or also called HCN channels.
The more negative the membrane potential is the more it activates.
As the membrane potential becomes more positive, Ca2+ channels will open. As more and more open a more steep curve will form and action potential will be reached.
There is then an inactivation of the Ca2+ channels and opening of voltage-gated K+ channels.
There is no plateau in this form of action potential.

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6
Q

Which part of the heart is fastest to depolarise? Which is next?

A

SA node is the fastest.

AV node is number two.

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7
Q

What is the term for an action potential that fire too slowly?

A

Bradycardia

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8
Q

What is the term for an action potential the fail?

A

Asystole

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9
Q

What is the term for an action potential that fire too quickly?

A

Tachycardia

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10
Q

What is the term for when the electrical activity becomes random?

A

Fibrillation

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11
Q

What is the concentration for hyperkalaemia?

A

[K+] at > 5.5 mmol/L

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12
Q

What is the concentration for hypokalaemia?

A

[K+] at < 3.5 mmol/L

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13
Q

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

A

Because K+ permeability is the dominant permeability in the resting membrane potential.
Because the heart has many different types of K+ channels that behave in different ways.

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14
Q

What are the effects of hyperkalaemia?

A

[K+] increase means that the resting membrane potential will become less negative. It depolarises the myocytes and slows down the upstroke for the action potential, this is because there is already some inactivation of Na+ channels. There is a less steep increase to the action potential and the action potential will not be as long.

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15
Q

What are risks with hyperkalaemia?

A
  • The heart can stop (asystole) as there is an inactivation of Na+ channels
  • It may initially increase excitability
  • Depends on the extent and how quickly it develops
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16
Q

How is hyperkalaemia treated?

A

Calcium gluconate or insulin + glucose

17
Q

What are the effects of hypokalaemia.

A

Compared to hyperkalaemia where the AP is shortened the AP is lengthened in hypokalaemia and repolarisation is delayed.

18
Q

Why can hypokalaemia be a problem?

A

The longer action potential can lead to early after depolarisation where oscillations in the membrane potential occurs. This can result in ventricular fibrillation.

19
Q

Briefly explain cellular mechanism of contraction in cardiomyocytes.

A
  • Depolarisation opens L-type Ca2+ channels in T-tubule system
  • Localised Ca2+ entry opens CICR channels in the SR meaning more Ca2+ is released into cytoplasm
  • Close link between L-type channels and Ca2+ release channels
  • 25% Ca2+ enters from sarcolemma, 75% is released from SR
  • Ca2+ then binds to troponin C and conformational change shifts tropomyosin to reveal myosin binding site on actin filament.
  • Myosin heads can now bind to actin and do stroking motion.
20
Q

How does calcium exit the cytoplasm?

A

Most Ca2+ is pumped back into SR via SERCA

Some exit across cell merman via Sacrolemmal Ca2+ ATPase and also NCX exchange.

21
Q

Briefly explain cellular mechanism of contraction in the vascular system.

A

Ca2+ binds to calmodulin which activates Myosin Light Chain Kinase (MLCK)
The MLCK phosphorylates the myosin light chain to permit an activated myosin head to interact with actin.
Relaxation occurs as Ca2+ levels decline. Myosin light chain phosphatase inactivates the myosin head once again and contraction stops.

22
Q

What can inhibit the action of MLCK?

A

Phosphorylation of the MLCK by PKA inhibits the action of MLCK.

23
Q

What is the effect of inhibiting MLCK?

A

Inhibition of contraction.