Electrical And Molecular Mechanisms Of Heart + Vasculature

Question 1

What transporter sets up the electrochemical gradient between Na+/K+ ?

Answer 1

Na+ / K+ ATP ase

Question 2

What ion channel sets up the resting membrane potential in cardiac myocytes ?

Answer 2

K+

Question 3

What makes the inside of a cardiac myocyte more negative with respect to the outside ?

Answer 3

Small movement of K+ ions out of the cell down their electrochemical gradient. And a High concentration of sodium outside the cell.

Question 4

Does resting membrane potential equal Equilibrium of K+ in a cardiomyocyte ?

Answer 4

No , because there is very small permeability to other ions at rest. For example chloride ions or sodium.

Question 5

What is the equilibrium potential of K ?

Answer 5

• 95mV

Question 6

What is the resting membrane potential loft a cardiac myocyte ?

Answer 6

-90 to -85 mV

Question 7

How does excitation of myocytes result in contraction of the cardiac muscle cells ?

Answer 7

Action potential triggers an increase in cytosolic Ca2+ which is required for the intercation between actin and myosin.

Question 8

Do cardiac potentials have long or short action potentials ?

Answer 8

VERY long - around 280 ms-300ms

Question 9

Outline the process of the VENTRICULAR cardiac action potential

Answer 9

1) when depolarisation reaches the myocytes , the threshold is reached (-80mv) VOltage gated sodium channels open. This allows an influx of Na+ into the cell.
2) the Action potential peaks around +20mv. This is where the voltage gated Na+ channels close ( become inactivated ). And there is some opening of the voltage gated K+ channels. This results in transient repolarisation which some K+ moving out of the cell.
3) L type voltage gated Ca2+ channels open which causes an influx of Ca2+ to move into the myocyte. This is demonstrated by the plateau as the efflux of K+ ions is counteracted by the influx of Ca2+ ions. This calcium is then used to cause muscular contraction.
4) once muscular contraction occurs , the L type voltage gated Ca2+ channels become inactivated. And more voltage gated K+ channels open to allow more K+ to move out of the cell and cause repolarisation.
5) the membrane potential then reaches -90mv. Voltage gated K+ channels inactivate. And the myocyte waits for the next wave of depolarisation.

Question 10

Do cardiac myocytes have the same type of K+. Channels ?

Answer 10

no , they have many different types of K+ channels where each one behaves in a different way.

Question 11

Outline the process of Sino atrial node action potential

Answer 11

1) When the membrane is hyperpolarised , there is the opening of the ‘ hyper-polarisation activated , cyclic nucleotide gated Na+ channels’ ( HCN). Opening of these causes slow movement of Na+ into the cell to cause the gradual depolarisation.
2) Once threshold is reached , L type Ca2+ channel open causing a fast influx of Ca2+ into the cell causing rapid depolarisation. The potential peaks at around 20mv where the L type Ca2+ channels inactivate.
3) the Voltage gated K+ channels now open and allow movement of K+ out of the cell to cause repolarisation.

Question 12

What is the funny current (If)

Answer 12

The slow depolarisation of the pacemaker cells of the SA node to the threshold potential.

Question 13

When is the depolarisation ( funny current) of Sino atrial cells initiated?

Answer 13

When the membrane is hyperpolarised after the previous action potential.

Question 14

If action potentials fire too slowly , what occurs ?

Answer 14

Bradycardia

Question 15

If action potentials fail what occurs ?

Answer 15

Asystole

Question 16

If action potentials fire too quickly , what occurs ?

Answer 16

Tachycardia

Question 17

If electrical activity becomes random , what occurs ?

Answer 17

Fibrillation

Question 18

What is normal plasma concentration of K+

Answer 18

3.5-5.5 mmol/L^-1

Question 19

What occurs when plasma levels of K+ drop below 3.5 mmol/L^-1?

Answer 19

• HYPOKALAEMIA

there is decreased K+ concentration outside of the cell.

• this means that there is a delayed repolarisation because the K+ do not work as effectively.
• this delay in repolarisation results in increased excitability of the myocytes as the action potential lasts much longer.

Question 20

What occurs when the plasma concentration of K+ increases above 5.5 mmol/L^-1?

Answer 20

Hyperkalaemia

Question 21

What occurs in hyperkalaemia?

Answer 21

• the concentration of K+increases outside the cell,
• this means there is a less of a concentration gradient of K+ across the myocyte cell membrane.
• this leads to the equilibrium potential of the K+ becoming less negative ( more Positive ). And so the membrane potential is more positive also.
• initially ( first few hours) , the resting membrane potential is closer to the threshold potential which means that the membrane is more likely to depolarise and so an action potential would fire much quickly. So heart rate would initially increase.
• however as we know , after depolarisation sodium channels inactivate and in order for them to activate again membrane potential must be reached again ( USUALLY -90mv). However in hyperkaemia the new membrane potential is -70 ish. So the sodium channels over time would become difficult to activate again. So over a long period of time heart rate would decrease as it would become difficult to depolarise the membrane.

Question 22

How do cardiomycotes contract ?

Answer 22

1) depolarisation opens up the L type Ca2+ channels in the T tubules.
2) localised Ca2+ entry opens the Calcium induces calcium release channels ( CICR) in the SR. Which causes more Ca2+ to enter the cell.
3) these Ca2+ then go on to bind to tropnin C. Which causes a conformational change which shifts tropomyosin to reveal myosin binding site on actin filament.

Question 23

How does relaxation of the cardiac myocytes occur ?

Answer 23

Must return intracellular Ca2+ levels back to normal

• most is pumped back into the SR via the sarcoendo plasmin recticilum ATPase.
• some exits across the cell membrane ( sarcolemma ca2+ ATPase and Na+/Ca2+ exchanger )

Question 24

Where is the smooth muscle found in vessels ?

Answer 24

Tunica media

Question 25

How does contraction of smooth muscle cells occur in the vascular system which allows constriction of the smooth muscle in the tunica media ?

Answer 25

1) depolarisation opens voltage gated calcium channels. This causes an influx of Ca2+. ANOTHER way of causing an increase in intracellular Ca2+ would be for noradrenaline for bind to a1 adrenoreceptors (gq). This would activate the enzyme phospholipase C which would hydrolyse PIP2 into IP3. IP3 is responsible for inducing the release of Ca2+ from the SR.
2) Ca2+ binds to CALMODULIN. ( 4 can bind to one )
3) The calcium - CALMODULIN copped activates The MYOSIN LIGHT CHAIN KINASE ( MLCK).
4) MYOSIN LIGHT CHAIN KINASE phosphorylates the myosin light chain to permit interaction with the actin.

Question 26

What occurs when Ca2+ levels decline in smooth muscle contraction ( vascular)?

Answer 26

Myosin light chain phosphatase dephosphorylases the myosin light chain.

Question 27

What helps to keep myosin head in active form in vascular smooth muscle cells ?

Answer 27

• when phospholipase C is activated- this hydrolyses PIP2 into DAG and IP3. DAG is used to activate protein kinase C which inhibits the myosin light chain phosphotase (MLCP)

Question 28

What are th consequences with hypokalaemia?

Answer 28

• longer action potentials could lead to early after depolarisations ( EADS)
• this can lead to oscillations in membrane potential.
• this can result in ventricular fibrillations.
• which can increase excitability of the heart.