L9: Electrical and molecular events Flashcards

1
Q

Which ion is responsible for setting up the membrane potential across a cell? How is it set up?

A

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

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2
Q

What is the equilibrium potential for K+? How does this compare to the resting membrane potential and why?

A

-95mV
RMP= -90mV
Small permeability to other ions

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3
Q

What are the cells in the heart called?

A

Cardiac myocytes

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4
Q

How does contraction of the muscle come about? (brief explanation)

A

Cardiac myocytes are electrically active–> conduct action potentials
Action potential leads to increased cytosolic Ca2+
Allow actin and myosin interaction–> contraction

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5
Q

How does the cardiac action potential compare to other ‘normal’ action potentials?

A

Duration much longer

280ms compared to 1-2ms in axons

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6
Q

What are the different phases of ventricular (cardiac) action potential?

A

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

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7
Q

What is the difference between the AP at the Sino atria node?

A

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

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8
Q

How does the action potential at the SA node occur?

A
  • -> 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
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9
Q

Why does it not open voltage gated Na+ channels?

A

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

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10
Q

What are the channels that are responsible for the funny current?

A
HCN channels (Hyperpolarisation-activated Cyclic Nucleotide-gated channels)
--> Influx of Na+ to depolarise cell
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11
Q

How does the action potential ‘spread’ across the heart?

A

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

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12
Q

If you don’t have a SA node what happens?

A

AV node takes over–> pacemaker–> slower than SA node

That fails–> other cells take over–> even slower AP

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13
Q

What is special about the SA node and AV node AP compared to the atrial muscle, purkinje fibres and ventricular muscle?

A

Unstable resting membrane potential
Unusual AP on graph
The rest look like normal ventricular myocyte AP however duration is different

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14
Q

What are some of the complication of action potentials?

A

Too slow–> Brachycardia
Fail –> Asystole
Too fast –> Tachycardia
Random –> Fibrillation

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15
Q

Why are the cardiac myocytes so sensitive to changes in concentration of K+?

A

Set up the resting membrane potential

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16
Q

What is hyperkalaemia? What does it cause?

A

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

17
Q

What are the risk associated with hyperkalaemia? How can it be treated?

A

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

18
Q

What is hypokalaemia? What does it cause?

A

Low K+ concentration <3.5mmol/L
Lengthens the AP
Delays repolarisation (K+ involved in repolarisation)

(less K+ outside, cells respond by reducing permeability)

19
Q

What are the problems associated with hypokalaemia?

A

Longer AP –> Early after depolarisation
Membrane oscillations –> repolarise and depolarise again–> ventricular fibrillation
(potentially the Ca2+ channels recover from inactivation so can be reactivated)

20
Q

How does excitation-contraction coupling work?

A
  • 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
21
Q

How do cardiac myocytes return to their resting state (NOT RMP)?

A

Ca2+ pumped back onto SR by SERCA or across membrane into extracellular space by Na+/Ca2+ exchanger or sarcolemma Ca2+ATPase

22
Q

What muscle is found in the walls of the vasculature? Which layer is it present in?

A

Smooth muscle

Found in the Tunica Media

23
Q

What controls vasoconstriction and dilation?

A

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

24
Q

What are the major difference between cardiac and smooth muscle for APs?

A

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)