9. Electrical And Moleculae Mechanisms In The Heart And Vasculature Flashcards
Describe how potassium sets the RMP in a cardiac myocyte?
Cardiac myocytes permeable to K+ ions at rest
K+ ions move out of cell down concentration gradient
Small movement of ions makes the inside negate with respect to the outside
Electrical gradient is established
What is the RMP of ventricular myocytes?
-90 to -85 mV
What is Ek?
-95mV
What do action potentials trigger in cardiac myocytes?
Increase in cytosolic [Ca2+]
Why is a rise in cytosolic [Ca2+] required?
To allow actin and myosin interactions Generates tension (contraction)
How many action potentials are required for a contraction?
1
How long are cardiac ventricle action potentials?
~280ms
What are the stages of ventricular action potential?
Opening of V-gated Na+ channels (depolarisation)
Transient outward K+ current (rapid repolarisation)
Oepning of V-gated Ca2+ channels (some K+ channels also open) - long lasting
Ca2+ channels inactivate V-gated K+ channels open (repolarisation)
Why do some K+ channels open when V-gated Ca2+ channels open?
To stop the membrane potential going too positive
What happens in the first part of the SAN action potential?
Pacemaker potential If
Influx of Na+
Long slow depolarisation to threshold
Funny current - more hyperpolarised, more they open
What happens in the second stage of the SAN action potential?
Opening of V-gated Ca2+ channels
What is the final stage of the SAN action potential?
Opening of V-gated K+ channels
What is the pacemaker potential?
Initial slope to threshold (funny current)
Activated at membrane potential more negative than -50mV
More negative, the more it activates
HCN channels allow influx of Na+ ions which depolarises the cells
Turning off of K+ current
What are HCN channels?
Hyperpolarisation-activated, Cyclic Nucelotide-gated channels
Sensitive to changes in cAMP
Which is the fastest action potential in the heart to depolarise?
SA node
What is the role of the SA node?
Sets rhythm
Is the pacemaker
Other parts of the conducting system also have automaticity but are slower
What happens if action potentials fire too slowly?
Bradycardia
What happens if action potentials fail?
Asystole
What happens if action potentials fire too quickly?
Tachycardia
What happens if electrical activity becomes random?
Fibrillation
What is the plasma K+ concentration range?
3.5-5.5 mmol/L
Why are cardiac myocytes so sensitive to changes in [K+]?
K+ permeability dominates resting membrane potential
The heart has many different kinds of K+ channels
What are the effects of hyperkalaemia?
Depolarises myocytes and slows down the upstroke of action potentials
If you raise plasma K+ then Ek gets less negative so the membrane potential depolarises a bit
This inactivates some of the voltage gated Na+ channels
What are the risks with hyperkalaemia?
Heart can stop - asystole
May initially get an increase in excitability - depolarisation means closer to threshold
Depends on extent and how quickly it develops
What is the treatment for hyperkalaemia?
Calcium gluconate - shields membrane, makes it less excitable
Insulin and glucose - drives potassium into cells
These won’t work if heart already stopped
What are the effects of hypokalaemia?
Lengthens the action potential
Delays repolarisation - happens more slowly
What are the problems with hypokalaemia?
Longer action potential can lead to early after depolarisations
Can lead to oscillations in membrane potential
Can result in ventricular fibrillation
Describe excitation-contraction coupling
Depolarisation opens L-type Ca2+ channels in T-tubule system
Localised Ca2+ entry opens calcium-induced calcium release (CICR) channels in SR
Most calcium is released form SR
Ca2+ binds to troponin C
Conformational change shifts tropomysoin to reveal myosin binding site on actin filament
What happens during relaxation of cardiac myocytes?
Return [Ca2+]i to resting levels
Most is pumped back into SR (SERCA)
Some exits across cell membrane
Describe the excitation contraction coupling in smooth muscle cells
Voltage gated Ca2+ channels open after depolarisation
Ca2+ binds to calmodulin (4 molecules)
Activates myosin light chain kinase (MLCK)
Phosphorylates myosin head and activates it
Myosin light chain phosphorylase (MLCP) removes phosphate form myosin
What is alternative method for Ca2+ to be released in smooth muscle cells?
Noradrenaline activates alpha 1 receptors with Gq protein in cell
Separates into IP3 and DAG
IP3 then acts on IP3 receptors on SR and causes Ca2+ release
DAG activates PKC which inhibits MLCP
