Flashcards in 4. Electrical and molecular events in the CVS Deck (18):
Describe how the resting membrane potential is set up in myocytes.
Mainly due to permeability to K+ ions:
- small movement of K+ ions out of the cell down their concentration gradient (inside of cell more negative than outside)
- charge movement out of cell causes an electrical gradient (wants to move K+ back into cell)
- net outflow of K+ until Ek is reached - no net movement as electrical and chemical gradients are equal and opposite
But resting MP (approx -85mV) not completely equal to Ek (-95 mV) due to very small permeability to other ion species.
Describe the extra- and intracellular ion concentrations for myocytes at rest.
Na+ 140 10
K+ 4 140
Ca2+ 1.2 0.0001
Cl- 120 30
What is the major difference between action potentials in heart cells and in neurons/skeletal muscle?
Length of depolarisation:
- 0.5 ms in neurons/skeletal muscle
- 100 ms in caridac muscle
How long is the cardiac AP? Why does this happen and why is this important?
- About 280 ms, because of the plateau sustained by the opening of voltage-gated Ca2+ channels.
- Length ensures that:
1. once the AP has begun in any part of the heart, the cell will be depolarised when the last cell in the myocardium starts its AP
2. muscular contraction in systole is sustained for 200-300 ms (duration is essential for normal pumping activity of the heart)
Describe the phases of the ventricular (cardiac) action potential.
0 : depolarisation (-85mV to 25mV)
- depolarisation to threshold... opening of voltage-gated Na+ channels... Na+ influx
1 : slight repolarisation (25mV to 5mV)
- transient outward K+ current
2 : plateau (5mV to -1mV)
- opening of voltage-gated Ca2+ channels... Ca2+ influx
- some K+ channels also open... small K+ efflux (balance to maintain plateau)
3 : repolarisation (-1mV to -85mV)
- Ca2+ channels inactivate
- voltage-gated K+ channels open... K+ efflux
4 : resting MP
What type of calcium channels are responsible for calcium influx in the plateau phase?
Describe the process of SA node action potentials.
1. Pacemaker potential (=long slow depolarisation to threshold, -60 mV to ~-40 mV)
- involves "funny current" - Na+ influx through slow HCN channels
2. Depolarisation (-40 mV to 20 mV)
- opening of voltage-gated Ca2+ channels... Ca2+ influx
3. Repolarisation (20 mV to -60 mV)
- opening of voltage-gated K+ channels... K+ efflux
*no proper resting potential in SA node
What is the pacemaker potential? How is it generated?
- Is the initial slope to threshold (funny current)
- Activated at MPs that are more negative than -50mV. The more negatived, the more it activates.
- Generated by the influx of Na+ (depolarises the cell) through HCN channels
What are HCN channels?
- Hyperpolarisation-activated Cyclic Nucleotide-gated channels
- Allow influx of Na+ ions
- Opened by binding of cAMP/GMP (so regulated by the ANS)
What are the differences between APs at pacemaker cells and ventricular myocytes?
Cardiac myocyte AP:
1. Initiated by conduction of excitation from neighbouring cell
2. Stable resting MP (-85mV) in diastole. No pacemaker potential
3. Have fast voltage-gated Na+ channels but no HCN channels
4. Depolarisation caused by fast voltage-gated Na+ channels
5. Have a plateau phase - sustained opening of Ca2+ channels
6. Has a resting MP (diastole)
Pacemaker cell AP:
1. Initiated by cell itself
2. Unstable resting MP - slow initial depolarisation from -60mV (most neg value) = pacemaker potential
3. Have HCN channels but no fast voltage-gated Na+ channels
4. Depolarisation caused by voltage-gated Ca2+ channels
5. No plateau phase - opening of Ca2+ channels not sustained
6. No resting MP
How does the AP spread from the SA node to the rest of the heart?
Via gap junctions between myocytes.
1. From SA node to AV node.
2. Delay at AV node to allow atrial contraction before ventricular contraction.
3. Down Bundle of His and into left and right bundle branches
Why are the SA node cells the pacemakers? Under which conditions would they not set the rhythm?
- Other parts of the conducting system also have automaticity, e.g.AV node, Purkinje fibres. But natural contraction rate is much slower.
- If there is a conduction block between SA node and rest of cell, other parts of conduction system can be important in setting rhythm.
What is wrong with the APs during: bradycardia, asystole, tachycardia and fibrillation?
Bradycardia: APs fire too slowly
Asystole: APs fail
Tachycardia: APs fire too quickly
Fibrillation: electrical activity becomes random
How does an AP lead to myocyte contraction?
1. Depolarisation opens L-type Ca2+ channels in T-tubule system.
2. Small Ca2+ influx (25%) stimulates opening of ryanodine receptors in SR and Ca2+ release from SR (75%) (= calcium-induced calcium release).
3. Ca2+ binds to troponin C... shifts tropomyosin to reveal myosin binding site on actin filament.
4. Etc of sliding filament mechanism,
How is relaxation of cardiac myocytes achieved?
Returning [Ca2+]i to resting levels:
- most is pumped back into SR via SERCA (stimulated by raised [Ca2+]i)
- some exits across cell membrane via sarcolemmal Ca2+ ATPase and Na+/Ca2+ exchanger
How is the tone of blood vessels controlled?
By contraction and relaxation of vascular smooth muscle cells, located in tunica media of arteries, arterioles and veins.
Describe the process of smooth muscle cell contraction.
1. Increased [Ca2+]i via 2 mechanisms.
a) depolarisation opens VGCCs
b) NA activates alpa1 R... Galpha q cleaves PIP2 to DAG and IP3... IP3 opens R on SR.
2. Calcium binds to CaM (4 Ca2+ for 1 CaM)... CaM binds to MLCK (myosin light chain kinase).
3. MLCK phosphorylates regulatory light chain of myosin II head.
4. Phosphorylated myosin II can interact with actin... contraction.
* Dephosphorylation of myosin light chain by MLCP (constitutively active) is prevents by inhibition by PKC (activated by DAG).