CVS 4 Electrical + Molecular Mechanims In Heart + Vasculature Flashcards
What sets the the resting membrane potential?
K+ permeability
How does K+ permeability set the resting membrane potential?
- K+ move out down conc. gradient until Ek is reached
- negative charge inside
- build up of charge creates an electrical gradient
What is the Ek?
Equilibrium potential for K+ ions
-95mV
What is the resting membrane potential valve?
-80 to -90mV
What do you get if the action potential fires too slowly?
Bradycardia
What do you get if the action potential fires too quickly?
Tachycardia
What do you get if the action potential fires randomly?
Fibrillation
What do you get if the action potential fails to fire?
Asystole
Explain the process of ventricular action potential
1- influx of Na+ - opening of VGNC - depolarisation
2- short efflux of K+ - transient outward K+ current - initial repolarisation
3- influx of Ca2+ - opening of VGCC- plateau
4- efflux of K+ - opening of VGKC- repolarisation
Hyperkalaemia meaning + value
High plasma K+ conc.
> 5.5mol/L
Hypokalaemia meaning + value
Low plasma K+ conc.
<3.5mol/L
Normal plasma K+ conc
3.5-5.5mmol/L
What is the effect of hyperkalaemia on ventricular AP?
- Some VGNC are inactive- slow upstroke
- Shorter AP?
- can stop heart if K+ conc is too high
Risks of hyperkalaemia
Asystole - heart stops if too high
Initial increase in excitability
Treatment of hyperkalaemia
Calcium gluconate
Insulin + glucose - control cell uptake of K+
What is the effect of hypokalaemia on ventricular AP?
- Lengthens AP
- Delays repolarisation - can cause early depolarisation > ventricular fibrillation
What are HCN channels?
Hyperpolarisation activated cyclic nucleotide gated channels
What is the funny current?
- Initial slow depolarisation by influx of Na+
- Pacemaker potential until threshold potential reached
Explain the SAN action potential
1- influx of Na+ - HCN channels - funny current
2- influx of Ca2+ - L type VGCC
3- efflux of K+ - VGKC
4- HCN channels open + cycle repeats
What sets the rhythm of the heart?
SAN
How is electrical activity of the heart initiated?
Spontaneous depolarisation
How does sympathetic activation increase heart rate?
- Release of noradrenaline + adrenaline
- Act on B1 adrenoreceptors on SAN cells
- Faster pacemaker potential
- Increased heart rate
Explain the process of excitation contraction coupling of smooth muscle
1- Ca2+ enter via VGCC or release from sacroplasmcic reticulum
2- Ca2+ binds to calmodulin
3- MLCK activation
4- MLCK phosphorylates myosin light chain
5- MLC interacts with actin
6- contraction occurs
7- Ca2+ levels fall
8- MLCP dephosphorylates MLC
What does calcium bind to in vascular smooth muscle?
Calmodulin
What does calcium bind to in cardiac myocytes
Troponin-C
What does MLCK stand for?
Myosin light chain kinase
What does MLCP stand for?
Myosin light chain phosphatase
What is depolarisation?
A change to a less negative potential
What is repolarisation?
A change to back to a negative potential
What is hyper polarisation?
A change to a more negative potential than the normal resting potential
What causes inactivation of VGNC in hyperkalaemia?
Membrane potential becoming less negative and cell depolarising