Cellular and molecular events COPY

Question 1

What sets up resting membrane potential?

Answer 1

K+ permeability

Cardiac myocytes permeable at rest

Question 2

Flow of K+

Answer 2

Na+K+ATPase sets up concentrations
K+ is high in cell so moves out of cell
Makes inside negative relative to outside

Question 3

Equilibrium potential for K+

Answer 3

When chemical and electrical gradients result in no net movement of K+

(Chemical gradient draws K+ out of cell, Negative electrical charge pulls K+ back into cell)

Question 4

Why is resting membrane potential not Ek?

Answer 4

Small permeability to other ions at rest

BUT K+ is main determinant of RMP

Question 5

Ek vs RMP

Answer 5

Ek = -95mV
RMP = -80 to -90mV

Question 6

Special features cardiac myocytes

Answer 6

Fire action potentials

Electrically coupled to allow syncronized contraction

Question 7

What does action potential trigger?

Answer 7

Increase in Ca2+ in cytoplasm

Question 8

What triggers action potential?

Answer 8

Depolarisation

Question 9

Whys is Ca2+ required?

Answer 9

Allows actin and myosin interaction (binds to Troponin C)

Question 10

Length of action potentials

Answer 10

SA node and Cardiac ventricle have much longer action potentials than axons/skeletal muscle

100ms vs 0.5ms

Question 11

Ventricular cardiac action potential steps

Answer 11

Depolarisation = opening of Voltage gated Na+ channels (curve goes positive)
Transient outflow of K+ (curve dips slightly negative)
Opening of Ca2+ channels = plateau (some K+ channels open)
Ca2+ channels inactivate, V gated K+ channels open (curve goes back to resting membrane)

Question 12

What causes depolarisation?

Answer 12

Opening of V gated Na+ channels

Question 13

What causes slight dip in membrane potetial? (initla repolarisation)

Answer 13

Transient outflow of K+

Question 14

What sustains plateau phase?

Answer 14

Open V gated Ca2+ channels

some K+ channels are open

Question 15

What causes repolarisation?

Answer 15

Ca2+ channels inactivate

V gated K+ channels open - K+ moves out

Question 16

3 phases of Ventricular action potential

Answer 16

Na+ influx
Ca2+ influx (K+ efflux)
K+ efflux

Question 17

SA node action potential difference

Answer 17

No stable Resting membrane potential
Slow depolarisation after each cycle
Na+ doesn’t cause fast depolarisation - Ca2+ does

Question 18

3 phases of SA node action potential

Answer 18

Pacemaker potential (If - funny current) from influx of Na+ (slow depolarisation)
Opening of V gated Ca2+ channels (fast depolarisation)
Opening of V gated K+ channels (repolarisation)

Question 19

Pacemaker potential job

Answer 19

Initial slope to threshold - funny current (If)

Activated at negative membrane potentials (lower than -50mV) - more negative more activation

Question 20

How does SA node achieve transient inflow of Na+?

Answer 20

HCN channels
Hyperpolarisation-activated Cyclic Nucleotide-gated channels
allow influx of Na+

Question 21

Types of Ca2+ channels SA node

Answer 21

L-type and Transient (T ) type

Question 22

How is upstroke achieved SA node?

Answer 22

Opening of V gated Ca2+ channels

Question 23

How is down stroke (repolarisation) achieved in SA node?

Answer 23

Opening V gated K+ channels (leaves)

Question 24

Innervation SA node

Answer 24

No innervation needed

Natural automaticity

Question 25

Membrane potential SA node

Answer 25

UNSTABLE (pacemaker potential, funny current)

Question 26

Action potentials through heart speed

Answer 26

SA node = fastest

Question 27

Action potential journey

Answer 27

``` SA node Across atria AV node Bundle of His Purkinje fibres Ventricle contraction ```

Question 28

Pacemaker of heart?

Answer 28

SA node | sets rhythm

Question 29

AP's through heart

Answer 29

SA node and AV node - fast | Atrial muscle, ventricular muscle and purkinje fibres - slower

Question 30

What is responsible for contraction?

Answer 30

Spread of action potential

Question 31

Problems with action potential firing

Answer 31

too slow - bradycardia fail - asystole too quickly - tachycardia random - fibrillation

Question 32

Hyperkalaemia

Answer 32

High plasma conc (>5.5mmol/L)

Question 33

Hypokalaemia

Answer 33

Low plasma conc (<3.5mmol/L)

Question 34

why are cardiac myocytes sensitive to change in K+?

Answer 34

k+ permeability dominates membrane potential

Question 35

Hyperkalaemia effects

Answer 35

Ek = less negative Membrane potential depolarises Inactivates some of Na+ channels Slows upstroke

Question 36

Risks hyperkalaemia

Answer 36

Heart stops - asystole | Initial increase in excitability (depolarised)

Question 37

Extent hyperkalaemia

Answer 37

Mild: 5.5 - 5.9 mmol/L Moderate: 6.0 - 6.4 mmol/L Severe: > 6.5mmol/L

Question 38

Treatment hyperkalaemia

Answer 38

Calcium gluconate Insulin and glucose (causes cells to uptake K+) **Heart needs to be pumping

Question 39

Effects of hypokalaemia

Answer 39

Lengthens action potential | Delays repolarisation

Question 40

Problems hypokalaemia

Answer 40

Longer action potentials can cause Early After Depolarisation (EAD's) Oscillations in membrane potential Ventricular fibrillation (remember shaking in hypothermia like osscilations)

Question 41

Excitation contraction coupling initial step

Answer 41

Depolarisation opens L type Ca2+ channels in T tubules

Question 42

What does Ca2+ entering cytosol cause in cardiac cells?

Answer 42

Opens Calcium induced calcium release (CICR) channels in SR

Question 43

What happens after CICR channels open?

Answer 43

Ca2+ binds to troponin C Conformational change shifts tropomyosin Binding site revealed on actin = myosin can bind

Question 44

How do cardiac myocytes relax?

Answer 44

Ca2+ pumped into SR (via SERCA) | Some exits via membrane (Ca2+ATPase, Na+Ca2+ exchanger)

Question 45

How is tone of blood vessels controlled?

Answer 45

Contraction and relaxation of vascular smooth muscle cells | tunica media, arteries arterioles and veins

Question 46

Excitation contraction coupling smooth muscle cells initial stimulation

Answer 46

Noradrenaline activates a1 receptors | or depolarisation opening V gated Ca2+ channels

Question 47

What does a1 receptor do?

Answer 47

Activates Gaq to produce second messanger IP3

Question 48

What does IP3 do?

Answer 48

Binds to receptors on sarcoplasmic reticulum | Initiates release of Ca2+

Question 49

What does Ca2+ once released from cell? (smooth muscle)

Answer 49

Binds to calmodulin

Question 50

what does calmodulin do?

Answer 50

Activates Myosin light chain kinase (MLCK)

Question 51

What does MLCK do?

Answer 51

Phosphorylates myosin light chain = allows interaction with actin

Question 52

How does contraction stop in smooth muscle?

Answer 52

Myosin light chain phosphatase dephosphorylates the myosin light chain PKA phosphorylates myosin light chain kinase = inactive

Question 53

How is contraction inhibited? (smooth muscle cell)

Answer 53

PKA (protein kinase A) phosphorylates MLCK and inhibits it

Question 54

Cardiac muscle vs smooth muscle excitation and contraction

Answer 54

Cardiac: Action potential allow Ca2+ entry More Ca2+ then comes from SR Ca2+ binds to TROPONIN C Smooth muslce: Depolarisation/activation of a-adrenoreceptors Increased intracellular Ca2+ Ca2+ binds to Calmodulin Activates MLCK - phosphorylates myosin light chain