Lecture 9 Flashcards
What sets up the resting membrane potential in cardiac myocytes?
K+ permeability (K+ channels open all the time)
- permable to K+ ions at rest, so they move out the cell down their concentration gradient
- this sets up an electrical gradient making the inside negative
- this pushes K+ back into the cell
- net outflow of K+ until Ek is reached
Why does RMP never equal Ek?
Because the membrane is permeable to other ions at rest
usually -90/-85, rather than -95
When does contraction occur?
excitation -> contraction
When every AP is fired,because AP triggers increase in cytosolic Ca2+, allowing contraction due to actin & myosin interaction.
(cardiac myocytes are electrically active-fire AP’s)
What is unusual about a cardiac AP?
It is very long, 280 ms.
compared to AP of an axon= 0.5ms
What are the stages of the cardiac action potential?
Resting potential: -85mV
- opening of V gated Na channels due to depolaristion, mV move towards Ena (+70mV) (these fast Na+ channels that cause the AP are very different to HCN’s causing pacemaker potential)
- transient outward K+ current (rapid & short lived)
- PLATEU PHASE: opening of L type voltage gated Ca2+ channels (also require some K+ channels opening to maintain the membrane potential)
- Ca2+ channels deactivate and voltage gated potassium channels open
What is special about L type voltage gated Ca2+ channels?
They stay open for a long time, hence why they are part of the plateu phase.
Why do each cardiac myocyte behave in a different way?
They have lots of different types of K+ channels.
What is the SA/AV node AP? (the pacemaker potential)
Resting potential: -60mV
- long slow depolarisation (PACEMAKER POTENTIAL) due to influx of Na+ (funny current: If) vis HCN channels
- spontaneous depolaristion without any nervous input
- T type (transient) Ca2+ channels open to reach TV (not Na+!!)
- opening of voltagegated K+ channels cause repolarisation
Does the AV/SA node depolarise more slowly?
AV node
What do SA node/pacemaker cells lack?
They have little Na+ channels
no plateau, AP is triangular, as soon as membrane is depolarised over TV, it starts to repolarise
When is the pacemaker potential activated?
At membrane potentials that are more -ve than -50mV
What are HCN channels?
Hyperpolarisation-activated, Cyclic Nucleotide-gated
- allow the influx of Na+ ions
- cAMP activates these channels
How do the SA node AP fire?
Natural automacity.
No nervous input, they do it automatically due to a mixture of ion channels giving an unstable membrane potential.
What is the purpose of the SAN?
Set the HR/rhythm
-it is the pacemaker
How does the purkinje fibres AP differ from the ventricular AP?
There is a slight depolarisation before the upstroke.
What is bradycardia/tachycardia?
Bradycardia- AP’s fire too slow (below 60)
Tachycardia- AP’s fire too quickly (above 100)
What is asystole/filbrillation?
Asystole- AP’s fail
Fibrillation- electrical activity becomes random
What is the plasma K+ concentration range?
3.5-5.5 mmol/L
Why are cardiomyocytes sensitive to changes in K+?
- heart has many different types of K+ channels
- K+ permeability dominates resting membrane potential
What is hyperkalaemia and its effects?
> 5.5 mmol/L
- raise plasma K+
- resting potential not as low
- inactivates some voltage gated Na+ channels, slowing the upstroke
Effects:
- asystole
- increased excitability
What are the different extents of hyperkalaemia?
Mild: 5.5-5.9 mmol/L (increased excitability)
Moderate: 6-6.4 mmol/L
Severe: 6.5 mmol/L +
Moderate and severe lead to asystole
How would you stop the heart for surgery?
Bathe in high potassium solution, and ice cold so doesn’t require oxygen.
What is the treatment for hyperkalaemia?
-calcium gluconate
-insulin/glucose (moves K+ into cell)
These don’t work if heart has already stopped because they can’t be transported around the blood.
What is hypokalaemia and its effects?
- K+ channels respond to low levels of plasma K+ by reducing its permeability to K+
- lengthens the AP as it delays repolarisation
Problem with hypokalaemia?
- longer AP can lead to early after depolarisations (EADs)
- leads to oscillations in the membrane potential
- results in ventricular fibrillation
How does excitation cause contraction of the muscle?
-depolarisation of T tubules opens L type Ca2+ channels
-Ca2+ entry opens Induced Calcium Release (CICR) channels in SR causing Ca2+ to be released into the muscle
-Ca2+ binds to troponin C
-conformational change causes tropomyosin to reveal myosin binding site on actin
= Reverse Sliding Filament Mechanism
How much Ca2+ comes from the SR/sarcolemma?
SR: 75%
Sacrolemma (t tubule): 25%
How do cardiac muscles relax?
Return to Ca2+ resting levels
- most pumped back into SR via SERCA (raised Ca2+ stimulates the pumps)
- some exits across cell membrane via Na+/Ca2+ exchanger, sarcolemmal Ca2+ ATPase
How are the blood vessels controlled?
Contraction/relaxation of smooth muscle layer in the tunica media
How does contraction of smooth vascular muscle occur?
- depolarisation opens voltage gated calcium channels/ NA activates alpha 1 G protein coupled receptors (which cleaves to IP3 & DAG, IP3 stimulates release of Ca2+ from ER)
- 4 Ca2+ bind to calmodulin, which activates MLCK
- MLCK phophorylates regulatory light chain on myosin head, forming ADP, activating it and allowing the myosin to attach to actin
What is MLCK & MLCP?
Myosin Light Chain Kinase
Myosin Light Chain Phosphatase
How does smooth vascular muscle relax?
- relaxation as Ca2+ levels decline
- MLCP removes phosphate from light chain to allow relaxation
What effect does DAG have on vascular smooth muscle contraction?
-PKC from DAG has an inhibitory effect on MLCP, keeping myosin in active form
What happens if MLCK is phosphorylated?
- phosphorylated by PKA
- inhibits MLCK, inhibiting phosphorylation of myosin light chain, and therefore contraction
What does increased tone of a vessel mean?
Refers to degree of constriction, so therefore narrowing the lumen in this case.
