Flashcards in CVS 4.1 - Cellular and Molecular Events of the Cardiovascular System Deck (36):
What is the resting membrane potential of cardiac myocytes?
What sets the resting membrane potential of cardiac myoctyes?
- Na+K+ATPase (establishes the gradient)
- Permeability of the membrane to K+ ions
How does Na+K+ATPase establish the gradient?
- Pumps out 3Na+ for every 2K+ pumped in (against gradients)
- Ensures there is always a +1 charge moving out so less ATP than expected is required
What would happen if Na+K+ATPase became blocked?
- Cell would become hyperpolarised due to the leakage of K+
- Increased number of closed Na+ channels causes a build up inside the cell
- NCX would become less effective which would increase cytosolic Ca2+
- Longer action potential as depolarisation would be sustained
How does the membrane's permeability to K+ ions contribute to the resting membrane potential of cardiac myocytes?
- K+ channels are open at rest so ions flow out down their gradient
- Intracellular charge is negative relative to the outside due to the positivity of K+
- K+ is the attracted to the -ve inside of the cell so flows in down its electrical gradient
- Gradients become balanced so there is no net movement of ions (Ek)
What causes the difference between RMP and Ek?
Permeability of the membrane to other ions
What happens to cause depolarisation of the ventricles?
Voltage gated Na+ channels open causing the membrane potential to move closer to Ena and therefore to threshold
What happens after the ventricles have depolarised?
- K+ voltage gated channels open
- Initial repolarisation due to the outward flow of K+
What happens after the initial repolarisation of the ventricles?
- Na+ channels deactivate
- Voltage gated Ca2+ channels (L-type) open causing a Ca2+ influx
- There is some K+ efflux
What causes the long plateau of the cardiac action potential?
- Ca2+ channels take longer to activate
- Causes long plateau due to prolonged depolarisation
What happens after the long plateau during the cardiac action potential?
- Increased intracellular Ca2+ caused CICR
- Cardiac myocytes contract
- Further efflux of K+ moves membrane potential further towards Ek
What is the funny current?
The long, slow depolarisation of the SAN
What causes the funny current?
- HCN channels/ Slow Na+ channels
- Become activated when the membrane potential becomes more negative than -50mv (hyperpolarisation)
- More negative = more activated
What happens in the SAN when the threshold is reached by the funny current?
- Voltage gated Ca2+ channels open
- Slow depolarisation due to Na+ being deactivated
How does the SAN repolarise?
- Voltage gated K+ channels open
- Repolarisation is caused due to K+ efflux
How do action potentials differ in the ventricles?
- Slower depolarisation
- Depolarisation is caused by opening of voltage gated Na+ channels
How do action potentials differ in the SAN?
- Reaches threshold first = faster depolarisation
- Sets rhythm
- Opening of Ca2+ channels causes depolarisation
What causes CICR from the sarcoplasmic reticulum during the action potential?
- Depolarisation of cardiac myocytes = L type voltage gated channels open causing a calcium influx
- T tubules are lined with L type channels
- Localised calcium entry into the cell causes CICR channels on the SR to open
- Increased localised calcium entry
What is the significance of the calcium influx into the myocyte?
Sustains depolarisation = longer action potential
How does the Ca2+ influx cause contraction of the cardiac muscle?
- Extracellular Ca2+ and Ca2+ from the SR bind to troponin C in the muscle
- Causes a conformational change which moves tropomyosin out of the actin binding site
What is the sliding filament theory?
- Tropomyosin is moved out of the actin binding site by troponin C
- Allows a myosin actin cross bridge to form
- Myosin dissociates from ADP + Pi and flexes
- Causes a power stroke as the myosin moves to a relaxed state
- ATP binds to myosin head causing it to dissociate from the actin
What are the three subunits of troponin and what are their functions?
- Troponin C - Ca2+-binding subunit
- Troponin I - inhibits ATP-ase activity of acto-myosin
- Troponin R - tropomyosin-binding subunit which regulates the interaction of troponin complex with thin filaments
What happens if Ca2+ and ATP are still available after the muscle has contracted?
- Process repeats
- Can lead to tetany
What is tetany?
Muscle spasms that occur at irregular intervals
What determines the force generated by the cardiac muscle when contracting?
- Number of cross bridges formed
- Cytosolic Ca2+ concentration
What causes diastolic dysfunction?
- Higher than normal Ca2+ levels
- Leads to an increase in force of contraction and plateau time
What causes systolic dysfunction?
- Lower than normal Ca2+ levels
- Leads to a decrease in force of contraction
What is systolic dysfunction?
Decrease in myocardial contractility
What is diastolic dysfunction?
Increase in myocardial contractility
What happens when the cardiac muscle relaxes after contraction?
- Ca2+ levels are returned to resting levels
- 75% is pumped back into the SR by SERCA
- 25% is pumped out into the extracellular space by NCX/Ca2+ATPase
What is tetanus? Does it affect cardiac muscle?
An infection that causes muscle spasms. It does not affect cardiac muscle
Why doesn't tetanus affect cardiac muscle?
- Cardiac muscle has a long absolute refractory period due to inactivation of Na+ channels during the plateau
- Can't depolarise again so can't transmit an action potential
- Less CICR = fewer contractions
How is tetany caused?
- Stimulus acts before the previous contraction finishes
- Get multiple action potentials without a refractory period
How is contraction of vascular smooth muscle caused?
- Noradrenaline binds to alpha-1 adrenoceptors coupled to Gq proteins
- Gq breaks down PIP2 into IP3 and DAG in the membrane
- IP3 causes increased calcium release from the SR
- 4Ca2+ binds to calmodulin which activates MLCK
- MLCK phosphorylates myosin light chain = enables myosin-actin cross bridges to form
How is contraction of the vascular smooth muscle stopped?
- DAG that is produced from PIP2 along with IP3
- DAG activates protein kinase C
- PKC phosphorylates myosin light chain phosphatase = inhibited