Cellular and molecular events COPY Flashcards
What sets up resting membrane potential?
K+ permeability
Cardiac myocytes permeable at rest
Flow of K+
Na+K+ATPase sets up concentrations
K+ is high in cell so moves out of cell
Makes inside negative relative to outside
Equilibrium potential for K+
When chemical and electrical gradients result in no net movement of K+
(Chemical gradient draws K+ out of cell, Negative electrical charge pulls K+ back into cell)
Why is resting membrane potential not Ek?
Small permeability to other ions at rest
BUT K+ is main determinant of RMP
Ek vs RMP
Ek = -95mV RMP = -80 to -90mV
Special features cardiac myocytes
Fire action potentials
Electrically coupled to allow syncronized contraction
What does action potential trigger?
Increase in Ca2+ in cytoplasm
What triggers action potential?
Depolarisation
Whys is Ca2+ required?
Allows actin and myosin interaction (binds to Troponin C)
Length of action potentials
SA node and Cardiac ventricle have much longer action potentials than axons/skeletal muscle
100ms vs 0.5ms
Ventricular cardiac action potential steps
Depolarisation = opening of Voltage gated Na+ channels (curve goes positive)
Transient outflow of K+ (curve dips slightly negative)
Opening of Ca2+ channels = plateau (some K+ channels open)
Ca2+ channels inactivate, V gated K+ channels open (curve goes back to resting membrane)
What causes depolarisation?
Opening of V gated Na+ channels
What causes slight dip in membrane potetial? (initla repolarisation)
Transient outflow of K+
What sustains plateau phase?
Open V gated Ca2+ channels
some K+ channels are open
What causes repolarisation?
Ca2+ channels inactivate
V gated K+ channels open - K+ moves out
3 phases of Ventricular action potential
Na+ influx
Ca2+ influx (K+ efflux)
K+ efflux
SA node action potential difference
No stable Resting membrane potential
Slow depolarisation after each cycle
Na+ doesn’t cause fast depolarisation - Ca2+ does
3 phases of SA node action potential
Pacemaker potential (If - funny current) from influx of Na+ (slow depolarisation) Opening of V gated Ca2+ channels (fast depolarisation) Opening of V gated K+ channels (repolarisation)
Pacemaker potential job
Initial slope to threshold - funny current (If)
Activated at negative membrane potentials (lower than -50mV) - more negative more activation
How does SA node achieve transient inflow of Na+?
HCN channels
Hyperpolarisation-activated Cyclic Nucleotide-gated channels
allow influx of Na+
Types of Ca2+ channels SA node
L-type and Transient (T ) type
How is upstroke achieved SA node?
Opening of V gated Ca2+ channels
How is down stroke (repolarisation) achieved in SA node?
Opening V gated K+ channels (leaves)
Innervation SA node
No innervation needed
Natural automaticity
Membrane potential SA node
UNSTABLE (pacemaker potential, funny current)
Action potentials through heart speed
SA node = fastest
Action potential journey
SA node Across atria AV node Bundle of His Purkinje fibres Ventricle contraction
Pacemaker of heart?
SA node
sets rhythm
AP’s through heart
SA node and AV node - fast
Atrial muscle, ventricular muscle and purkinje fibres - slower
What is responsible for contraction?
Spread of action potential
Problems with action potential firing
too slow - bradycardia
fail - asystole
too quickly - tachycardia
random - fibrillation
Hyperkalaemia
High plasma conc (>5.5mmol/L)
Hypokalaemia
Low plasma conc (<3.5mmol/L)
why are cardiac myocytes sensitive to change in K+?
k+ permeability dominates membrane potential
Hyperkalaemia effects
Ek = less negative
Membrane potential depolarises
Inactivates some of Na+ channels
Slows upstroke
Risks hyperkalaemia
Heart stops - asystole
Initial increase in excitability (depolarised)
Extent hyperkalaemia
Mild: 5.5 - 5.9 mmol/L
Moderate: 6.0 - 6.4 mmol/L
Severe: > 6.5mmol/L
Treatment hyperkalaemia
Calcium gluconate
Insulin and glucose
(causes cells to uptake K+)
**Heart needs to be pumping
Effects of hypokalaemia
Lengthens action potential
Delays repolarisation
Problems hypokalaemia
Longer action potentials can cause Early After Depolarisation (EAD’s)
Oscillations in membrane potential
Ventricular fibrillation
(remember shaking in hypothermia like osscilations)
Excitation contraction coupling initial step
Depolarisation opens L type Ca2+ channels in T tubules
What does Ca2+ entering cytosol cause in cardiac cells?
Opens Calcium induced calcium release (CICR) channels in SR
What happens after CICR channels open?
Ca2+ binds to troponin C
Conformational change shifts tropomyosin
Binding site revealed on actin = myosin can bind
How do cardiac myocytes relax?
Ca2+ pumped into SR (via SERCA)
Some exits via membrane (Ca2+ATPase, Na+Ca2+ exchanger)
How is tone of blood vessels controlled?
Contraction and relaxation of vascular smooth muscle cells
tunica media, arteries arterioles and veins
Excitation contraction coupling smooth muscle cells initial stimulation
Noradrenaline activates a1 receptors
or depolarisation opening V gated Ca2+ channels
What does a1 receptor do?
Activates Gaq to produce second messanger IP3
What does IP3 do?
Binds to receptors on sarcoplasmic reticulum
Initiates release of Ca2+
What does Ca2+ once released from cell? (smooth muscle)
Binds to calmodulin
what does calmodulin do?
Activates Myosin light chain kinase (MLCK)
What does MLCK do?
Phosphorylates myosin light chain = allows interaction with actin
How does contraction stop in smooth muscle?
Myosin light chain phosphatase dephosphorylates the myosin light chain
PKA phosphorylates myosin light chain kinase = inactive
How is contraction inhibited? (smooth muscle cell)
PKA (protein kinase A) phosphorylates MLCK and inhibits it
Cardiac muscle vs smooth muscle excitation and contraction
Cardiac:
Action potential allow Ca2+ entry
More Ca2+ then comes from SR
Ca2+ binds to TROPONIN C
Smooth muslce:
Depolarisation/activation of a-adrenoreceptors
Increased intracellular Ca2+
Ca2+ binds to Calmodulin
Activates MLCK - phosphorylates myosin light chain
