Electrical and molecular events Flashcards
What are cardiomyocytes permeable to the most?
K+
What are cardiomycoytes slightly permeable to?
Na+
Ca2+
What is the resting membrane potential of cardiomyocytes?
-85 to -90mV
How do cardiac action potentials differ to axon action potentials?
Have a longer duration
How many phases are there in the ventricular action potential? What are they called?
Five phases
phase 0, 1, 2, 3, 4
What hapens in phase 0?
Depolarisation to theshold
VG Na+ channels open
Rapid influx of Na+
Rapid depolarisation
What voltage does the membrane depolarise to in phase 0? What is this called?
Above 0mV
Called the overshoot
What happens to VG Na+ channels after they open?
They inactivate
What happens in phase 1?
VG K+ channels open
Efflux of K+
Transient repolarisation
What happens in phase 2?
VG Ca2+ channels open
Influx of Ca2+
Balances with K+ efflux
No change in membrane potential
What happens in phase 3?
VG Ca2+ channels inactivate
More VG K+ channels open
More K+ efflux than Ca2+ influx
Repolarisation
What happens in phase 4?
Resting membrane potential
How long is spent in phase 4? Why?
Twice as long as phase 0+1+2+3
Because diastole is twice as long as systole
How long is the ventricular action potention?
Approx 400ms
Is there more than one type of K+ channel in cardiomyocytes?
Yes!
How are the K+ channels in cardiomyocytes different to each other?
Behave differently
How are the SA node myocytes specialised?
Can spontaneously depolarise
Do the SA node myocytes have a resting membrane potential? Why?
No
membrane potential is always changing
because they can spontaneously depolarise
What is the most negative membrane potential of SA node myocytes?
-60mV
What is the pacemaker potential?
The initial depolarisation of the myocyte to threshold
What type of channel is responsible for the pacemaker potential?
Hyper-polarised cyclic nucleotide-gated channels (HCN) channels
When do HCN channels open?
When the membrane potential is more negative than -50mV
When do an increased number of HCN channels open?
The more negative the membrane potential, the more HCN channels that open
What are HCN channels permeable to?
Na+
K+
What happens in the pacemaker potential phase?
HCN channels open
Na+ influx
Slow depolarisation
Why is there more Na+ influx than K+ in the open HCN channels?
Higher driving force for Na+
membrane potential is further away from ENa+
What happens in the upstroke of the SA node action potential?
Depolarisation to threshold VG Ca2+ channels open
Influx of Ca2+
Depolarisation of membrane
Why don’t VG Na+ channels open in the upstroke of the SA node action potential?
Because they will have opened during the pacemaker potential
And inactivated
Won’t open again till membrane has been repolarised
What happens in the downstroke of the SA node action potential?
VG K+ channels open
K+ efflux
Repolarisation
How long is the SA node action potential?
Approx 200ms
What sets the rhythm of the heart beat?
The SA node
What is it called when the SA node sets the rhythm of the heart beat?
Sinus rhythm
Why does the SA node set the rhythm of the heart beat normally?
Fastest to spontaneously depolarise
Which other cells in the heart can spontaneously depolarise?
AV node myocytes
Purkynje fibres
What would set the rhythm of the heart beat if their was a problem with the SA node?
The next fastest to spontaneously depolarise
What happens to action potentials in a heart beat?
They spread all over the myocardium
What causes bradycardia?
Pacemaker cells firing action potentials too slowly
What causes tachycardia?
If pacemaker cells fire action potentials too quickly
What causes asystole?
Failure of pacemaker cells to generate action potentials
What causes fibrillation?
Action potentials spread through heart muscle randomly
What is normal plasma K+ conc.?
3.5 - 5.5 mmol/L
What is hypokalaemia?
Plasma K+ conc below 3.5mmol/L
What is hyperkalaemia?
Plasma K+ conc. above 5.5.mmol/L
Why are cardiomyocytes sensitive to changes in plasma K+ conc.
Because K+ permability dominates the resting membrane potential
Cardiomyocytes has mnay different types of K+ channels, behave differently
How does hyperkalaemia affect the ventricular action potential?
Slows down upstroke of action potential
Narrows action potential
Why does hyperkalaemia slow down the upstorke of the action potential?
Increased extracellular K+ Less K+ diffuses out Builds up in cell Depolarises membrane slightly Inactivates Na+ channels Less available for upstroke
What is the risk of hyperkalaemia?
Asystole - heart stops contracting
How can hyperkaelaemia lead to asystole?
Inactivates enough VG Na+ channels
Lack of sufficient upstroke in SA node potential
Why might hyperkalaemia give an initial increase in excitability?
Due to depolarising membrane slightly
Closer to threshold
How long does the initial increase ine excitability last?
Till the VG Na+ channels inactivate
What do the effects of hyperkalaemia depend on?
The extend of hyperkalaemia
How quickly it developed
What is mild hyperkalaemia?
5.5 - 5.9 mmol/L
What is moderate hyperkalaemia?
6.0 - 6.4 mmol/L
What is severe hyperkalaemia?
More than 6.4 mmol/L
How is hyperkalaemia treated?
Calcium gluconate
Insulin and glucose
How does the insulin and glucose treatment work?
Insulin promotes potassium uptake by cells
Glucose to prevent hypoglycaemia by insulin
When will these treatments not work with hyperkalaemia? Why not?
In asystole
won’t be circulated around the body
How does hypokalaemia affect the ventricular action potential?
Delays repolarisation
lengthening the action potential
What is the risk of hypokalaemia?
Early after depolarisations (EADs)
Why do EADs occur?
Ca2+ channels been reactivated before repolarisation is complete
Influx of Ca2+
How do EADs affect the membrane potential?
Give oscillations in membrane potential
What can EADs lead to?
Ventricular fibrillation
What controls the tone of blood vessels?
Vasoconstriction - contraction of smooth muscle cells
Vasodilation - relaxation of smooth muscle cells
In smooth muscle cells of blood vessels, what does Ca2+ do once its entered a cell?
Four Ca2+ bind to one calmodulin molecule
What does calcium bound calmodulin do?
Binds to Myosin Light Chain Kinase (MLCK)
What effect does Ca2+-calmodulin binding to MLCK have?
Activates MLCK
What does activated MLCK do?
Phosphorylates the regulatory light chain
Where does the phosphate come from?
ATP hydrolysis to ADP
releases Pi
What effect does phosphorylation of the regulatory light chain have?
Activates myosin head
What can the active myosin head do?
Bind to actin
What happens to the intracellular Ca2+ conc during smooth muscle relaxation?
Decreases
What is MLCP?
Myosin light chain phosphatase
What does MLCP do during relaxation of smooth muscle?
Dephosphorylates the regulatory light chain
What effect does dephosphorylation of the regulatory light chain have?
Inactivates myosin head
What can the inactivated myosin head not do?
Bind to actin
What effect does PKC have?
Inhibits MLCP
Regulatory light chain not dephosphorylated
Myosin head remains active
How active is MLCP?
Constantly active
unless something inhibits it
What effect does PKA have on smooth muscle contraction/relaxation?
PKA phosphprylates MLCK
What effect does phosphorylation have on MLCK?
Inhibits MLCK
Regulatory light chain not phosphorylated
Myosin head is inactive
