L9: Electrical and molecular events Flashcards
Which ion is responsible for setting up the membrane potential across a cell? How is it set up?
K+ ions
Permeable to K+ ions at rest
Move out of cell down conc gradient
Make external slightly more +ve compared to inside (-ve)
Charge builds up forming an electrical gradient
What is the equilibrium potential for K+? How does this compare to the resting membrane potential and why?
-95mV
RMP= -90mV
Small permeability to other ions
What are the cells in the heart called?
Cardiac myocytes
How does contraction of the muscle come about? (brief explanation)
Cardiac myocytes are electrically active–> conduct action potentials
Action potential leads to increased cytosolic Ca2+
Allow actin and myosin interaction–> contraction
How does the cardiac action potential compare to other ‘normal’ action potentials?
Duration much longer
280ms compared to 1-2ms in axons
What are the different phases of ventricular (cardiac) action potential?
Phase 4: RMP set up by background K+ channels
Phase 0: Upstroke= Voltage gated Na+ channels open allowing influx of Na+
Phase 1: Initial repolarisation= K+ channels open transient outward K+ channels (V-gated i to)
Phase 2: plateaus due to L-type voltage gated Ca2+ channels, Ca2+ influx balanced with K+ efflux
Phase 3: rapid repolarisation, voltage gated K+ channels open, efflux of K+, Ca2+ channels inactivated
What is the difference between the AP at the Sino atria node?
Completely different action potential
Natural automaticity
Long slow depolarisation –> pacemaker potential
Cells never rest
No neuronal input–> only required for setting rate but SAN cells still ‘beat’ without them
How does the action potential at the SA node occur?
- -> I(f) - funny current–> influx of Na+ ions–> long slow action potential, activated at more negative MP than -50mV (more negative= more activation)–> depolarisation of membrane (Hyperpolarisation-activated Cyclic Nucleotide channels (HCN))
- -> Depolarise to threshold –> does NOT open Voltage gated Na+ channels
- -> Depolarisation also involves turning off of K+ current and Transient (T type) and L type Ca2+ channels
- -> Upstroke –> Voltage gated Ca2+ channels open
- -> Repolarisation/ Downstroke–> Opening of voltage gated K+ channels
- -> continuous, doesn’t get near Ek
Why does it not open voltage gated Na+ channels?
Cells don’t go negative enough to open them
Long slow depolarisation would put Na+ channels into inactive state and AP wouldn’t continuously fire
What are the channels that are responsible for the funny current?
HCN channels (Hyperpolarisation-activated Cyclic Nucleotide-gated channels) --> Influx of Na+ to depolarise cell
How does the action potential ‘spread’ across the heart?
AP spreads across the atria to AV node
AV node–> slight delay–> allow atria sytole
Down Bundle of His –> right and left bundle branches
Along purkinje fibres–> base of heart–> contraction from base upwards
If you don’t have a SA node what happens?
AV node takes over–> pacemaker–> slower than SA node
That fails–> other cells take over–> even slower AP
What is special about the SA node and AV node AP compared to the atrial muscle, purkinje fibres and ventricular muscle?
Unstable resting membrane potential
Unusual AP on graph
The rest look like normal ventricular myocyte AP however duration is different
What are some of the complication of action potentials?
Too slow–> Brachycardia
Fail –> Asystole
Too fast –> Tachycardia
Random –> Fibrillation
Why are the cardiac myocytes so sensitive to changes in concentration of K+?
Set up the resting membrane potential
What is hyperkalaemia? What does it cause?
Plasma–> Too high K+ concentration >5.5 mmol.L-1
Increased K+, Ek get less -ve –> cells depolarise a bit
Less efflux of K+ ions because the concentration gradient is less steep so more positive K+ remain inside the cell
Some Na+ channels become inactivated–> slowing the action potential
What are the risk associated with hyperkalaemia? How can it be treated?
Heart can stop–> asystole
Initially increase in excitability
Response depends on how fast it develops and the severity
High levels of hyperkalaemia–> more Na+ inactivation–> slows the AP down
Treatment–> done whilst alive
–> calcium gluconate–> Ca2+ makes membrane less excitabile
–> Insulin Glucose–> Insulin drives potassium into cells, glucose stops glucose levels droppoing
What is hypokalaemia? What does it cause?
Low K+ concentration <3.5mmol/L
Lengthens the AP
Delays repolarisation (K+ involved in repolarisation)
(less K+ outside, cells respond by reducing permeability)
What are the problems associated with hypokalaemia?
Longer AP –> Early after depolarisation
Membrane oscillations –> repolarise and depolarise again–> ventricular fibrillation
(potentially the Ca2+ channels recover from inactivation so can be reactivated)
How does excitation-contraction coupling work?
- AP–> depolarisation down T tubules–> opens L type Ca2+ channels
- Ca2+ influx–> opens CICR channel in SR
- -> 25% Ca2+ across sarcolemma, 75% from SR
- Ca2+ binds to troponin C–> conformational change–> tropomyosin moves uncovers myosin binding site on actin filament…. sliding filament theory
How do cardiac myocytes return to their resting state (NOT RMP)?
Ca2+ pumped back onto SR by SERCA or across membrane into extracellular space by Na+/Ca2+ exchanger or sarcolemma Ca2+ATPase
What muscle is found in the walls of the vasculature? Which layer is it present in?
Smooth muscle
Found in the Tunica Media
What controls vasoconstriction and dilation?
Smooth muscle contraction and relaxation
- Depolarisation opens VOCC
- Ca2+ binds to calmodulin
- Ca2+-calmodulin complex
- Activated MLCK
- Phosphorylates regulatory light chain in myosin
- Activated myosin allowing cross bridge formation
OR
- Noradrenaline activate alpha 1 receptors
- GPCR –> Galpha q subunit released
- Activated Phospholipase C–> PIP2–> DAG and IP3
- IP3–> Ca2+ release from SR –> Ca2+-calmodulin complex…
OR
- DAG activates Protein Kinase C –> inhibits MLCP –> keeps myosin head in active form
Relaxation
- MLCP –> dephosphorylates myosin light chain inactivating it–> constitutively active
What are the major difference between cardiac and smooth muscle for APs?
Cardiac
–> Ca2+ binds to troponin-C
–> Ca2+ input due to VOCC
Smooth muscle
–> Ca2+ bind to Calmodulin–> activate MLCK
–> Ca2+ influx either due to voltage operated Ca2+ channels or noradrenaline on alpha 1 (GPCR)
