S4) Cellular & Molecular Events in the CVS Flashcards
In four steps, describe how the resting membrane potential of cardiac cells is generated
⇒ Cardiac myocytes are permeable to K+ at rest
⇒ K+ move out of the cell (down concentration gradient)
⇒ Inside becomes more negative relative to the outside
⇒ As charge builds up an electrical gradient is established
In three steps, briefly explain how excitation leads to action
⇒ Cardiac myocytes are electrically active & fire action potentials
⇒ Action potential triggers increase in [Ca2+]i
⇒ Actin and myosin interact, triggering the contraction mechanism
State the RMP for the following:
- Axon
- Skeletal muscle
- SAN
- Cardiac ventricle
Describe the 4 different stages of the ventricular (cardiac) action potential
- Depolarisation – Na+ influx
- Initial repolarisation – K+ efflux
- Plateau – Ca2+ influx
- Proper repolarisation – K+ efflux
Describe the 3 different stages in the SAN action potential
Describe the mechanisms behind the slow depolarising pacemaker potential
- Turning on of slow Na+ conductance (If – funny current)
- Activated at membrane potentials more negative than - 50mV
- HCN (Hyperpolarisation-activated Cyclic Nucleotide-gated) channels are activated which allow influx of Na+ for depolarisation
Describe how the action potential waveform varies throughout the heart
- SAN is fastest to depolarise, it is the pacemaker and sets rhythm
- Other parts of the conducting system also have automaticity, but it’s slower
Describe the action potential diagrams for different parts of the heart:
- SAN
- Purkinje fibres
- Atrial muscle
- Ventricular muscle
- AVN
Explain four problems that could occur during the process of excitation leading to contraction
- Action potentials fire too slowly → bradycardia
- Action potentials fail → asystole
- Action potentials fire too quickly → tachycardia
- Electrical activity becomes random → fibrillation
What is the normal range of plasma [K+]?
3.5 – 5.5 mmol L-1
If [K+] is too high or low it can cause problems, particularly for the heart.
In terms of plasma [K+] levels, define hyperkalaemia and hypokalaemia
- Hyperkalaemia – plasma [K+] is too high > 5.5 mmol.L-1
- Hypokalaemia – plasma [K+] is too low < 3.5 mmol.L-1
In 5 steps, describe the effects of hyperkalaemia
⇒ EK becomes less negative (smaller concentration gradient)
⇒ Membrane potential becomes less negative and depolarises
⇒ Early depolarisation causes Na channels to open then inactivate (less steep uptake slope)
⇒ HCN channels are activated by hyperpolarisation (remain inactive)
⇒ Depolarisation is slow and over a long duration
What are the risks associated with hyperkalaemia?
- Pacemaker potential decreases, heart rate decreases/stops (asystole)
- May initially get an increase in excitability but then conductance may cease
Risks associated with hyperkalaemia depend on the extent and how quickly it develops.
Describe the severity of hyperkalaemia
- Mild: 5.5 – 5.9 mmol/L
- Moderate: 6.0 – 6.4 mmol/L
- Severe: > 6.5 mmol/L
How can hyperkalaemia be treated?
- Calcium gluconate
- Insulin + glucose
Ineffective if the heart already stopped
In 4 steps, describe the effects of hypokalaemia
⇒ EK becomes more negative (greater concentration gradient)
⇒ Membrane potential becomes more negative
⇒ Action potential is prolonged as plateau phase is longer (Ca2+ channels remain open)
⇒ Repolarisation is delayed & slower
What are the risks associated with hypokalaemia?
- Longer action potentials lead to early after depolarisations (EADs)
- Prolonged plateau phase provides greater opportunity to stimulate more action potentials and cause more contractions
⇒ Leads to oscillations in membrane potential which result in ventricular fibrillation
In two steps, describe excitation-contraction coupling
⇒ Depolarisation opens L-type Ca2+ channels in the T-tubule system
⇒ Localised Ca2+ entry opens closely-linked CICR channels in the SR
25% enters across sarcolemma, 75% released from SR
How does relaxation occur in cardiac myocytes?
[Ca2+]i must return to resting levels:
- SERCA is stimulated and pumps calcium back into SR
- PMCA & NCX remove calcium across the cell membrane
What controls the tone of blood vessels?
Tone of blood vessels is controlled by contraction & relaxation of vascular smooth muscle cells:
- Located in tunica media
- Present in arteries, arterioles and veins
In 5 steps, describe the cellular mechanism leading to the contraction of blood vessels
⇒ Ca2+ binds to calmodulin
⇒ Ca2+- calmodulin complex is formed
⇒ Myosin Light Chain Kinase is activated
⇒ MLCK phosphorylates myosin so it interacts with actin
⇒ Contraction mechanism is triggered
In 5 steps, describe the cellular mechanism leading to the relaxation of blood vessels
⇒ Ca2+ levels decline
⇒ Myosin light chain phosphatase dephosphorylates myosin
⇒ PKA phosphorylates MLCK & inhibits its action
⇒ Myosin light chain is not phosphorylated
⇒ Contraction is inhibited
pacemaker cells
specialised myocytes that generate electrical events in regular intervals = initiate an action potential
- diastole/most negative it depolarises at -60mv
- FUNNY (If) current as they open with hyperpolarisation
- HCN Channels =Hyperpolarisation-activated,Cyclic,Nucleotide-gated channels allow influx of Na ions to deoplarise the cell
conducting fibres
purkinje fibres conduct excitation through ventricular mycocardium
basis of resting membrane potential
due to the selectively permable membrane to K ions
For all cells, but pacemaker cells depolarisation spreads throughout the cells = threashold reached and then more Na ions enter
= action potential spreads
The Cardiac action potential
- longer than a nerve and striated muscle due to Ca channels
- action potential is passed through each cell via gap junctions
- one action potential = one heaartbeat
- after AP calcium ions leave cell and Na enters
- force of contraction relies on rate of removal and uptake of ca ions
