Cellular and Molecular Events in the CVS

Question 1

Does Na/K-ATPase set the RMP?

Answer 1

No

Question 2

What happens to RMP if the sodium pump is blocked?

Answer 2

It only changes by 5-7mV

Question 3

What is the RMP set by?

Answer 3

Due to K permeability of the cell membrane at rest

Question 4

What state are K channels in at rest?

Answer 4

Open

Question 5

What channels do cardiac myocytes possess?

Answer 5

Inward rectifier K channels

Question 6

How permeable to other ions are cardiac myocytes?

Answer 6

Only a small permeability

Question 7

What can be said of cardiac myocytes?

Answer 7

They are electrically active

Question 8

What is meant by cardiac myocytes being electrically active?

Answer 8

They fire action potentials

Question 9

What do action potentials trigger?

Answer 9

An increase in cytosolic [Ca]

Question 10

What is a rise in calcium required for?

Answer 10

To allow actin and myosin interaction

Question 11

What does actin and myosin interaction generate?

Answer 11

Tension (contraction)

Question 12

How do action potentials in heart cells differ from those in nerves and skeletal muscle?

Answer 12

They are much longer

Question 13

What are the stages in the ventricular (cardiac) action potential?

Answer 13

Opening of voltage gated Na channels causes a rapid depolarisation, from RMP to +30mV as Na enters the cell
Transient outward K current causes a return towards a lower membrane potential, reaching +10mV
Membrane potential lowers to about -10mV because of opening of voltage gated Ca channels
Ca channels inactivate and voltage gated K channels open, causing return to RMP

Question 14

What is rapid depolarisation due to opening of Na channels called?

Answer 14

The upstroke

Question 15

What might happen after the initial depolarisation that contributes to a lower membrane potential?

Answer 15

Might get some reversal of Na/Ca transport

Question 16

What may also happen when the voltage gated Ca channels are open?

Answer 16

May be some K channels open, allowing efflux of K

Question 17

What do cardiac myocytes possess lots of different types of?

Answer 17

K channels

Question 18

Draw the ventricular action potential

Answer 18

Answer…

Question 19

Why do cardiac myocytes have lots of different types of K channels?

Answer 19

Because they each behave in a different way, and contribute differently to the electrical properties of the cell

Question 20

What is the SA nodes set membrane potential?

Answer 20

Doesn’t really have one

Question 21

Why does the SA node not really have a set membrane potential?

Answer 21

Because the whole time, there is a long, slow depolarisation

Question 22

What is the SA nodes long, slow depolarisation called?

Answer 22

The pacemaker potential

Question 23

What causes the pacemaker potential?

Answer 23

Influx of Na

Question 24

What happens as Na channels open?

Answer 24

Na ions go in to cause a little bit of depolarisation, but become inactivated in accommodation due to long depolarisation

Question 25

What is the result of the Na channels becoming inactivated by the long depolarisation?

Answer 25

The upstroke cannot rely on Na channels, it also needs voltage gated Ca channels

Question 26

What is the initial slope to threshold of the SA node action potential known as?

Answer 26

The funny current

Question 27

When is the SA node action potential activated?

Answer 27

When it reaches membrane potentials that are more negative than -50mV

Question 28

What is the result on the SA node action potential when the membrane potential reaches a more negative level?

Answer 28

The more it activates

Question 29

What channels does the funny current use?

Answer 29

HCN

Question 30

How are HCN channels activated?

Answer 30

Hyperpolarisation

Question 31

How are HCN channels controlled?

Answer 31

Cyclic nucleotide-gated

Question 32

What do HCN channels allow?

Answer 32

Influx of Na ions, which depolarises the cell

Question 33

Describe the process of the SA node action potential

Answer 33

Voltage gated Ca channels when the membrane potential reaches -50mV, causing depolarisation  Opening of voltage gated K channels cause repolarisation

Question 34

What does the opening of voltage gated Ca channels cause in the SA node action potential?

Answer 34

Upstroke

Question 35

What does the opening of voltage gated K channels cause in the SA node action potential?

Answer 35

Downstroke

Question 36

How does the SA node action potential differ from the ventricular?

Answer 36

It is not as quick

Question 37

Why is the SA node action potential not as quick as the ventricular?

Answer 37

Because calcium channels open more slowly

Question 38

What is the SA node action potential said to have?

Answer 38

Natural automaticity

Question 39

What is said of the membrane potential of the SA node?

Answer 39

It is unstable

Question 40

Does the action potential waveform stay the same throughout the heart?

Answer 40

No, it varies

Question 41

What part of the heart is fastest to depolarise?

Answer 41

SA node

Question 42

What is the result of the SA node being the fastest to depolarise?

Answer 42

It sets the rhythm

Question 43

What other parts of the conduction system have automaticity?

Answer 43

AV node

Question 44

Why doesn’t the AV node set the rhythm?

Answer 44

It depolarises slower

Question 45

What path does the cardiac action potential take?

Answer 45

Travels from SA node, to AV node, down bundle of His to bundle branches

Question 46

What are the bundle branches in the heart?

Answer 46

Left (posterior division) Left (anterior division) Right

Question 47

What are the features of cardiac muscle?

Answer 47

Striated  Branching pattern  Intercalated discs  Single central nuclei

Question 48

How are cardiac muscle cells joined?

Answer 48

Structurally by desmosomes  | Electrically by gap junctions

Question 49

What do desmosomes do?

Answer 49

Rivet cells together

Question 50

What do gap junctions do?

Answer 50

Allow for rapid transfer of ions

Question 51

What does depolarisation that happens during the ventricular action potential do?

Answer 51

Opens L-type Ca channels in the T-tubule system

Question 52

Where is the T-tubule system localised?

Answer 52

Close to the SR

Question 53

What does localised Ca entry due to channels opening cause?

Answer 53

Opening of calcium-induced calcium release (CICR) channels in the sarcoplasmic reticulum

Question 54

What is closely linked to L-type channels?

Answer 54

Ca release channels

Question 55

What % of calcium enters across the sacrolemma, through L type channels?

Answer 55

25%

Question 56

What % of calcium is released from the SR?

Answer 56

75%

Question 57

How is cardiac myocyte contraction regulated?

Answer 57

Ca binds to troponin C, and a conformational change shifts tropomyosin to reveal myosin binding site on actin filament

Question 58

What must happen to relax cardiac myocytes?

Answer 58

Must return intracellular [Ca] to normal levels

Question 59

How is intracellular [Ca] returned to normal levels?

Answer 59

Most pumped back into SR | Some exits across plasma membrane

Question 60

How is Ca pumped back into the SR?

Answer 60

SERCA

Question 61

What stimulates the SERCA pumps?

Answer 61

Raised [Ca]

Question 62

How does Ca exit across the cell membrane?

Answer 62

Sarcolemmal Ca-ATPase | Na/Ca exchanger

Question 63

What is tone of blood vessels controlled by?

Answer 63

Contraction and relaxation of vascular smooth muscle cells

Question 64

Where are the vascular smooth muscle cells located?

Answer 64

In the tunica media

Question 65

What is present in the tunica media?

Answer 65

Multiple circularly arranged smooth muscle layers

Question 66

What vessels have vascular smooth muscle cells?

Answer 66

Arteries, arterioles and veins

Question 67

How is vascular smooth muscle different from striated muscle?

Answer 67

Don’t have the same arrangement of actin and myosin

Question 68

How are actin and myosin arranged in vascular smooth muscle?

Answer 68

Connected to dense bodies, and radiate out

Question 69

At what level does regulation of cardiac contraction occur?

Answer 69

Of the myosin head

Question 70

How does the myosin head regulate cardiac contraction?

Answer 70

It has a regulatory light chain

Question 71

What happens when light chain on the myosin head is not phosphorylated?

Answer 71

It can’t bind to actin

Question 72

How is myosin activated?

Answer 72

Myosin light chain kinase (MLCK) phoshorylates myosin

Question 73

Why does MLCK need to be controlled itself?

Answer 73

To prevent it from activating myosin all the time, and contraction happening all the time

Question 74

How is MLCK controlled?

Answer 74

Calmodulin

Question 75

How does calmodulin activate MLCK

Answer 75

Calmodulin can bind 4 calcium ions. Calcium can either come from voltage gated calcium channels, or from SR. In smooth muscle cells, there are adrenoreceptors- α-1 receptors. If noradrenaline binds these receptors, it causes production of IP 3 which then causes release of calcium from SR. Calcium binds to calmodulin, which activates MLCK.

Question 76

How is MLCK activation terminated?

Answer 76

Myosin light chain phosphatases

Question 77

When are MLCPs active?

Answer 77

Constitutively- active all the time

Question 78

How are MLCPs regulated?

Answer 78

When noradrenaline binds to alpha-1 receptor, also forms DAG, which activates protein kinase C- phosphorylates MLCP, inhibiting it.

Question 79

Why is there relaxation as Ca levels decline?

Answer 79

As myosin light chain phosphatase dephosphorylates the myosin light chain (no longer inhibited as noradrenaline not binding)