CVS - Electricals Flashcards
What is the funny current?
Slow inward current of Na+ that is activated at membrane potentials more negative than -50mV
What is different about some characteristics of the SAN AP compared to a ventricular myocyte?
- Spontaneous
- Funny current
- Unstable membrane potential
- No fast Na channels (slow upstroke)
- Upstroke is Ca2+ channels not Na+
What is the pacemaker potential?
Stage 4 - slow depolarisation to threshold of VOCCs
At what mV do T and L type Ca2+ channels open in the SAN AP?
T -50mV
L - -40mV
What are the funny current channels called?
HCN - Na+ channels
Why is the SAN pacemaker of the heart?
As it is the fastest cell type in the hear to depolarise so sets the rhythm.
Why is the heart particularly susceptible to a change in K+ plasma conc?
- Cardiac membrane potential is particularly sensitive to K (close to EK+) so a change in the EC K+ conc will change the membrane potential
- Many types of K+ channels in heart and some behave in peculiar ways
What effect does high plasma K+ conc have on the heart?
Asystole
What is the effect of hyperkalaemia on the ventricular AP?
Will shorten AP
Will depolarise myocyte - so slowing the upstroke of the AP and inactivating some of the Na+ channels - less Na channels available to contribute to the AP
What might you see with hyperkalaemia before asystole? How do you you treat hyperkalaemia? Why wouldn’t this treatment work in asystole?
May see a temporary increase in excitability
Treat with calcium gluconate - reduces excitability of myocytes so decreases the risk of arrhythmias
Wouldn’t work in asystole as needs to be pumped around the body
What are the effects of hypokalaemia on the ventricular AP?
Lengthens AP
Causes EADs (probably due to reactivation of Ca2+ channels)
Oscillations in MP
VF
What happens when an AP arrives at a cardiac myocyte?
1) Arrives via GAP junction
2) At T tubules - activates VOCCs (L type Ca channels/DHP receptors (same thing))
3) Ca2+ influx (25%)
4) Activated RyRs (close link with DHPRs)
5) CICR - Ca2+ binds with troponin C on tropomyosin and conformation change moves tropomyosin away from the myosin binding site on actin - myosin head binds etc.
What is normal plasma K+ concentration kept between?
3.5 - 5.5mM/L-1
What are the 4 stages of the sliding filament theory?
1) High energy configuration - Myosin attached to ADP + Pi and head is cocked - attaches to the actin filament
2) Working stroke - ADP and Pi released as myosin head pivots and bends and moves the actin filament towards the M line 5nm
3) Low energy configuration - ATP binds to myosin and the cross bridge detaches
4) Release of Pi causes the cocking of myosin head
What mechanisms return the IC Ca2+ levels back to normal post AP?
- SERCA (most)
- Na Ca ATPase
- NCX
Also calmodulin has an enhancing effect on Ca Na ATPase
How does excitation contraction coupling occur in SMCs?
1) Depol opens VOCCs
2) Ca2+ in binds to CaM - activates it
3) CaM binds to MLCK and activates it
4) MLCK phosphorylates the light chain of myosin head (increases its ATPase activity
5) This enables myosin binding to actin and can slide across
6) Myosin dephosphorylated by MLCPhosphatase
What is the relevance of the regulatory light chain on the myosin head in SMC contraction?
It must be phosphorylated to allow actin-myosin binding for contraction to occur
How can SMC contracted be inhibited?
By phosphorylation of MLCK by PKA - inhibits phosphorylation of the MLC and therefore inhibits contraction - inhibits GalphaS GPCR via beta 2 adrenergic receptor on SMC e.g. some blood vessels
(contraction is via alpha adrenergic receptors e.g. on vessel walls)
Which enzyme is constitutively active MLCK or MLCP? How can it be inhibited and what happens?
MLCP is - inhibited by PKC (G-alpha q GPCR alpha adrenoceptor) - so releases the activity of MLCP and allows MLC to be phosphorylated –> contraction
What is the effect of vagus nerve acting at M2 receptors on the heart?
Decreased HR (negative chronotropic effect) Decreased AVN conduction velocity (negative dromotropic effect)
Vagus nerve has most effect on SAN and AVN but also decreases ionotropy (force of contraction) and luisitropy (relaxation)
What is the effect of the parasympa and sympa nervous system on pacemaker potentials?
Sympa - increases the slope of pacemaker potential - increases rate of depol
Para - decreased the slope of the pacemaker potential - decreases rate of depol
How does sympa increase slope of pacemaker potential and how does para decrease it?
Sympa - via G alpha S GPCR cAMP
Para - via G alpha I GPCR decreased cAMP and increases K+ conductance
How does sympa NS increase ionotropy in the heart? (force of contraction) (3)?
1) Phosphorylation of Ca2+ channels increases Ca2+ entry during plateau phase of AP - more RyRs activated
2) Increased uptake of Ca2+ in SR so more released to bind to troponin C
3) Increased sensitivity of contractile machinery to Ca2+
Do vessels receive parasympathetic input?
Not really - only erectile tissue
