cardiovascular: Initiation of heartbeat

Question 1

differences in neuronal AP vs cardiac AP

Answer 1

neuronal AP: <1ms; short refractory period

cardiac AP: 350-380ms; long refractory period

Question 2

parts of cardiac AP

Answer 2

depolarisation (vertical increase): Na influx
plateau phase (gently slopes downwards): Na channels inactivate; Ca channels open (maintaining AP); slow activation of outward K currents 
repolarisation: K channels open

Question 3

why is the cardiac AP so long? what are the implications of a short refractory period?

Answer 3

prevents tetany/protects against re-entrant arrhythmias;

AP triggered rapidly one after another/tetany

Question 4

order of pacemakers in heart, from fastest to slowest

Answer 4

SA-> AV-> His bundles-> purkinje fibres

Question 5

SA nodal cells appearance; how does their structure support their function

Answer 5

poorly differentiated/no cytoplasm/ lots of membrane/ lots of cavaeolae (invaginations of membrane)
good for generating AP, not contracting

Question 6

2 theories about the pacemaker clock

Answer 6

membrane: regular pulse produced by cyclical changes in ionic currents
calcium clock: cyclic release of ca from intracellular stores

Question 7

characteristics of funny current: what is it/what carries it/what is it stimulated and inhibited and blocked by

Answer 7

it's the inward current that is activated when membrane HYPERPOLARISES (its funny because normally inward current is activated when membrane DEPOLARISES); 
inward current carried by Na and K;
activated by adr 
inhibited by ach 
blocked by ivabradine

Question 8

shapes of AP in atrial vs ventricular pacemakers

Answer 8

SEE SLIDES; atrial: upside down U

ventricular: vertical line-> downward slope increasing in gradient

Question 9

speed of conduction from SA-> AV-> his/purkinje; why is it like that

Answer 9

SA-> AV and through AV is slow (AV pause): allows ventricular filling/ prevents transmission of impulses at high rates from atria
AV-> his/purkinje is fast: allows apex of heart to contract before the base

Question 10

features of ventricular myocytes and how they contribute to their function

Answer 10

interdigitation/syncitium: mechanical strength/ good conduction of impulses
intercalated disks: contain gap junctions made of connexons (allow movement of ions/e-) -> anisotropic conduction (impulse travels fast ALONG fibres instead of ACROSS)

Question 11

whats a cardiac dipole?

Answer 11

wave of positiveness moving down from base to tip of heart, as heart becomes more + as it depolarises and - as it repolarises

Question 12

limb lead 2

Answer 12

right arm (reference)
left foot (recording)

Question 13

ECG waves

Answer 13

P: atrial depolarisation
Q: depolarisation of septum
R: depolarisation of ventricles (towards apex)
S: depolarisation of ventricles (towards atria)
T: repolarisation of ventricles (towards endocardium)

Question 14

explain Q wave

Answer 14

slow conduction through AV node-> pause (PQ interval)
bundle of His-> left and right branches @interventricular septum
depolarisation of first bit of interventricular septum from left to right (away from recording electrode) -> negative deflection on ECG

Question 15

explain R wave

Answer 15

bulk of interventricular septum + ventricular wall depolarises (towards recording electrode), facilitated by purkinje fibres-> positive deflection on ECG

Question 16

explain S wave

Answer 16

depolarisation of ventricles towards atria (away from recording electrode)-> negative deflection on ECG

Question 17

explain T wave

Answer 17

whole ventricle is depolarised-> no net movement of charge-> ECG @ isoelectric line
blip of T wave due to REPOLARISATION

Question 18

Which part of ECG corresponds to which part of cardiac AP

Answer 18

QRS: depolarisation + plateau
T: repolarisation

Question 19

how does [ca] rise with electrical activation

Answer 19

100nM -> 1microM in 30ms

Question 20

explain cardiac excitation-contraction coupling

Answer 20

involves Ca induced Ca release
AP down into T tubules-> voltage gated L type Ca channels open-> Ca enters and accumulates in dyadic cleft-> RyR senses small [ca] increase-> release of more Ca from SR (Ca induced Ca release) -> ca binds to sarcomere

Question 21

how is intracellular Ca removed during relaxation

Answer 21

SERCA (sarcoplasmic calcium ATPase) : returns Ca back into SR; regulated by accessory protein phospholamban
Na/Ca antiporter: surface membrane antiporter returns Ca extracellularly

Question 22

definitions of chronotropy/inotropy/lusitropy

Answer 22

chronotropy: heart rate
inotropy: strength of contraction
lusitropy: rate of relaxation

Question 23

examples of positive chronotropic agents and their effects

Answer 23

adrenaline/NA;

increase funny current-> faster diastolic depolarisation -> faster heart rate

Question 24

examples of a negative chronotropic agent and its effects

Answer 24

ach;
opens Kach channels-> membrane is more positive-> decreases funny current-> slower rate of diastolic depolarisation-> slower heart rate

Question 25

examples of a positive inotropic and lusitropic agent

Answer 25

isoprenaline

Question 26

stimulation of B1-adrenoreceptor (cardiac)

Answer 26

B1 agonist binds to adrenoreceptor (a GPCR)-> alpha subunit exchanges GDP for GTP-> activates adenylyl cyclase-> ATP converted into cAMP-> cAMP activates PKA-> PKA phosphorylates proteins using ATP

Question 27

PKA phosphorylation targets and effects

Answer 27

L-type Ca channels-> +chronotropy/inotropy
membrane/ca clocks-> +chronotropy
ATPase subunits eg phospholamban (SERCA regulatory protein)-> increased SR uptake-> +lusitropy
RYR2-> increased SR Ca release-> +inotropy
troponin I/myosin binding protein-> increased cross-bridge cycling-> +inotropy/lusitropy