initiation of heartbeat

Question 1

difference between speed for neuronal and cardiac action potential

Answer 1

neuronal - short <1mesc

cardac - longer 250msec

Question 2

what maintains the plateau phase of a cardiac action potential

Answer 2

Ca channels opening and entering

K channels opening and slowly leaving

Question 3

describe cardiac action potential

Answer 3

1) Na enters rapidly
2) K out
3) plateau - a enters
4) drops: Na and Ca transported out by Na/k ATPase and Na/Ca exchanger protein (respectively)

Question 4

Explain the difference between the lengths of action potentials for cardiac and skeletal muscle

Answer 4

• skeletal muschas short refractory periods to allow discrete contraction which are v close together. Contract with temporal summation, unfused tetanus or fused tetanic contractions
• cardiac: cannot tetanise cardiac muscle due to long refractory

Question 5

list the cardiac pacemakers from fastest to slowest

Answer 5

sinus node, AV node, His bundle, Purkinje fibres

Question 6

describe SA node

Answer 6

• highest intrinsic rate (drives the prevailing rate and overdrives the tissues downstream from it.)
• designed to generate action potential, not cause contraction

Question 7

describe the 2 pacemaker theories

Answer 7

1) membrane clock: cyclical changes in ion currents, mainly Na and K. stimulated by adrenaline, inhibited by acetylcholine and blocked by ivabradine
2) calcium clock: release of Ca from intracellular stores. Regulates pacemaker, drives membrane potential up and down diastole

Question 8

why is there slow conduction from SA to AV nodes

Answer 8

• allow ventricular filling

- filter out high frequencies so ventricles don’t beat too fast

Question 9

describe the layout of cells in ventricular muscle

Answer 9

conduction ALONG the length of cells.

intercalated disks give good strength and good conduction.

Question 10

what are at the gap junctions of intercalated disks

Answer 10

connexons (protein channels) formed by connexins

• allow small molecules and electrical currnts to pass
• at ends of cells as conduction occurs mostly along cell. Anisotropic conduction?

Question 11

describe Eithoven’s triangle and the different ways of taking measurements

Answer 11

• formed by 2 shoulder and groin - pick any 2 corners
• limb lead I: L arm to R arm
• limb lead II:L foot to R arm: classic ECG shape
• Limb lead III: L foot to L arm
• bipolar (recording and reference electrode) and augmented leads (recording and virtual)

Question 12

what could go wrong with PQ interval and whats the pathology

Answer 12

atrial conduction and AV node delay

AV block

Question 13

what could go wrong with QRS duration and whats the pathology

Answer 13

ventricular contraction velocity.

bundle branch block

Question 14

what could go wrong with ST interval and whats the pathology

Answer 14

heterogeneity of ventricular polarisation - all of ventricle depolarised.
myocardial infarction

Question 15

what could go wrong with QT interval and whats the pathology

Answer 15

ventricular action potential duration

Long QT syndrome

Question 16

where does Ca entering the myocyte accumilate

Answer 16

dyadic cleft - gap between SR and T-tubule

Question 17

key difference between cardiac and skeletal muscle Ca release

Answer 17

cardiac: CALCIUM-induced Ca release
skeletal: VOLATAGE-induced

Question 18

describe the relaxation of the action potential in the myocyte

Answer 18

1) Ca removed from cytosol by active transport - Sarcoendoplasmic Calcium ATPase (SERCA)
2) small amount entered through L channels is removed by Na/Ca exchangers

Question 19

what regulated the activity of SERCA

Answer 19

phospholamban

Question 20

what’s resting intracellular Ca

Answer 20

100mM

Question 21

explain chronotropy and give examples

Answer 21

Heart rate.

• positive chronotropy = increase HR, e.g.adrenaline, nor-adrenaline: increase funny current = faster rate of diastolic depolarisation
• Negative chronotropy, e.g. acetylcholine. decrease If, opens K (ACh) channels, slower HR

Question 22

what is intropy

Answer 22

strength/force of contraction.

Question 23

explain lusitropy and give clinical examples

Answer 23

rate of relaxation of cardiac muscle.

• heart failure = unable to take up ca.
• diastolic dysfunction - heart doesnt relax between pumps. HFpEF: heart failure with a preserved ejection fraction. diastolic.

Question 24

examples of positive intropy and lusitropy

Answer 24

• positive: Beta-1 receptor stimulation - adrenaline and NA.

- isoprenaline - B1 agonist. B1 stimulation acts via Gs and PKA

Question 25

what are the PKA targets and explain the effects

Answer 25

1) pacemaker
2) L-type Ca channels:
3) RYR2
4) ATPase subunits
5) myofilaments

Question 26

what are the both of the pacemaker theories inhibited/stimulated by

Answer 26

-both stimulated and inhibited by neurotransmitters (NA and ACh)

Question 27

what does PKA do to pacemaker cells

Answer 27

cAMP and PKA increase pacemaker currents = positive chronotropy

Question 28

what does PKA do to L-type channels

Answer 28

PKA phosphorylates L- type Ca channels and increases channel opening.
more Ca enters
positive chonotropy and intropy

Question 29

what does PKA do to ATPase subunits (on SR)

Answer 29

PKA phosphorylates phospholamban (PLB) and phospholemman (PLM)
- increases SR Ca uptake and cellular Na extrusion
– positive lusitropy

Question 30

what does PKA do to myofilaments

Answer 30

phosphorylates troponin I and myosin binding protein C and increases rate of cross bridge cycling
– faster contraction (inotropy)
- faster relaxation (lusitropy)

Question 31

what does PKA do to RYR2

Answer 31

phosphorylates RyR2 and increases SR Ca release

– positive inotropy

Question 32

what is membrane clock stimulated, inhibited and blocked by

Answer 32

adrenaline
ACh
ivabradine

Question 33

what is a role of the calcium clock model

Answer 33

regulate pacemaker