Cardiac Electrophysiology Flashcards
What are the three electrophysiologc types of cardiac cells?
- pacemaker cells (SA node, AV node)
- specialized rapidly conducting tissues (Purkinje fibers)
- ventricular and atrial muscle cells
[Na+] and [Ca++] are normally {higher/lower} outside the cell and [K+] is {higher/lower} inside the cell?
[Na+] and [Ca++] are normally higher outside the cell and [K+] is **lower **inside the cell
Extracellular Na+ concentration in myocytes is 145mM, and 15 mM inside
Extracellular [K+] is 5 mM and internal is [K+] 150 mM
Extracellular [Ca++] is 2mM, internal is 10^-7 M
External [Cl-] is 120mM, internal is 5 mM
What is the resting potential of the cardiac muscle cell?
About -90mV
What happens during Phase 0 of the cardiac action potential?
At rest, Na and Ca channels closed.
Stimulation -> Na channels open and Na+ enters the cell -> depolarization (cell less negative) -> even more Na+ channels open -> membrane potential becomes positive
What happens during Phase 1 of cardiac action potential?
small repolarization - K+ leak channels move K+ out of the cell, membrane potential reaches about 0 mV
What happens during Phase 2 of cardiac action potential?
K+ continues to “leak” outside the cell
Ca++ channels open and Ca++ enters the cell
K+ out balances Ca++ in, so no net change in charge is observed (hence plateau)
Ca++ is slower to open then Na+, hence it is in Step 2 (but remains open longer).
This is the crucial step in which Ca++ enters the cell to start myocardial contraction.
K+ outward rate slowly starts exceeding Ca++ in rate, leading to Phase 3
What happens in Phase 3 of cardiac action potential?
K+ outward rate slowly starts exceeding Ca++ in rate, leading to Phase 3, repolarization (action potential more -ve).
K+ continues to move out of the cell, all other channels become relatively inactive - > cell becomes negative again .
Ca++ is moved out of the cell via Na+ /Ca++ exchanger and ATP-linked Ca pump (less)
Na+/K+ is corrected via Na+/K+ ATPase
What happens during Phase 4 of cardiac action potential?
Phase 4 is known as resting phase - depolarization starts with phase 0.
What cardiac cells do not need external signal to initiate action potential?
Pacemaker cells are automatic - they spontaneously depolarize during phase 4. As they depolarize, threshold is eventually reached and action potential begins.
Pacemaker cells include: SA node and AV node. Atrial and ventricular myocytes can show automaticity when under stress, ex. ishemia.
What is a refractory period?
Absolute refractory period - time during which muscle cells are not responsive to any new stimulus.
Relative refractory period - stimulus can trigger action potential, but the rate of action potential is much slower then usual, since some of the Na+ channels are still inactivated, while some leak K+ channels are activated - less charge travelling.
Which cells have shorter refractory periods, ventricular or atrial?
Atrial cells have shorter refractory periods than ventricualr muscle cells, so during bad arrhythmias, atrial compression rates can be faster.
Where does cardiac depolarization start in the heart? Outline the sequence of tissues involved in propagation?
Electrical action potential initiated at the SA node -> spreads through atria via gap junctions -> AV node -> bundle of His, Purkinje fibers -> ventricular muscle cells
What are myosin, actin and troponin?
Myosin = thick filaments, contains heads
Actin = thin filament, double helix, covered with double helix of tropomyosin and dots of troponin. Think actin ~ active = thin
Tropomyosin = double helix that covers actin, inhibits direct contact between actin and myosin “tripping myosin”
Troponin = three circular subunits
TnT = links troponin to actin and tropomyosin
TnI = inhibits ATPase of actin-myosin
TnC = binds calcium
What links electical to mechanical contractility in cardiac muscle?
Ca++ links electrical and chemical contraction in myocardium. During phase 2 of the action potential, Ca++ flows into the cell . This [Ca++] is not enough to start cardiac contraction, but this increase in [Ca++] triggers sarcoplasmic reticulum (SR) of muscle cells to release more [Ca++].
How does mechanical contractility happen in cardiac cells?
Electrical action potential -> some Ca++ flows into the cell during Phase 2 ->
[Ca++] increase inside the cell stimulates ryanodine receptors in sarcoplasmic reticulum, which undergo conformational change - > more [Ca++] released, this time from SR->
now [Ca++] in cytosol is high enough to generate contraction
initial inflow of Ca++ via travelling action potential is amplified via activation of ryanodine receptors in SR, which lead to more Ca++ flow, stimulating contraction. This Ca++ amplyfing signal to increase [Ca++] in the cytosol is known as calcium-induced calcium release.
Ca++ binds to TnC (troponin), activity of TnI is inhibited, this induces conformational change in tropomyosin -> active site of actin is exponsed -> myosin heads bind to actin and “flex”, causing the move between thin and thick filaments (ATP-dependent)
What are the steps of the contractile process?
Ca++ binds to TnC (troponin), activity of TnI is inhibited, this induces conformational change in tropomyosin -> active site of actin is exponsed -> myosin heads bind to actin and “flex”, causing the move between thin and thick filaments (ATP-dependent)
see image for more details
Memory aid: Myosin is a cheat, if ATP is available it would prefer it to actin, but when ATP looses its assets and becomes ADP-P, myosin goes for actin instead. Once ATP becomes available again, myosin leaves actin again.
As cytosol Ca++ falls Ca++ leaves TnC and tropomyosin slides back onto binding sites of actin.
How does Ca++ leave cell/cytosol after contraction?
Ca++ that entered cell leaves cell via Na+/Ca++ exchanger (mostly) and Ca++-ATPase pump.
Ca++ that entered cytosol from SR returns to SR primarily through sarco (endo) plasmic reticulum Ca++ ATPase (SERCA).
Outline electrolyte concentration and ion channel types in cardiac cell?
What is a positive iotropic effect?
As beta-adrenergic receptors are stimulated, heart muscles contract with more force and contract faster = +ve inotropic effect.
What is positive lucitrophic effect?
an increase in the rate and duration of muscle relaxation of the cells following beta adrenergic stimulation = +ve lucitrophic effect.
Notice that you’re spending less type in systole now and more on relaxation / dyastole – need time for ventricular filling and flow of blood through coronary capillaries. When heart contracts, it can compress and shut down its vessels, so need to make sure you have enough time in dyastole to get O2 and remove CO2.
How do cardiac cells decrease systole and increase dyastole during beta-adrenergic stimulation?
[Ca++] in cytosol is key to regulating force of contraction. beta-adrenergic stimulation is one mechanism to change [Ca++] in the cytosol.
catecholamines (ex. norepinephrine) bind to beta1-adrenergic receptor (G protein coupled) -> ATP-cAMP -> inactive protein kinases -active protein kinases-> go on to phosphorylate:
- voltage-gated Ca channel within the membrane - increases influx of Ca++ into the cell -> ryanodine responds by coordinating more Ca++ released from SR -> force of contraction increased
- phospholamban (PL) is a protein in the SR membrane, which inhibits SERCA pump. Phosphorylation of phospholamban stops its inhibition, so SERCA pumps Ca++ back into SR faster -> myocytes relax faster. Notice that Na/Ca pump and Ca ATPases are not phosphorylated, they pump Ca++ out at the same rate, so we’re bringing more Ca++ into the cell, and it is going to SR via SERCA -> more Calcium exits into cytosol during action potential -> more Ca binds to troponin C -> higher force of contraction
- troponin also gets phosphorylated, which in turn decreases its affinity to Ca, so myosin and actin are more likely to detach from each other -> myocytes relax faster
Describe energy usage in cardiomyocyte?
Energy is in the form of ATP
If we shut off all production, all ATP would disappear in 10 seconds.
Sources of ATP are:
• Phosphocreatine (rapidly available) – during systole, your creatine phosphate can be broken down into ATP and creatine; probably enough for 2-3 beats
• Glycolytic pathway – about 20% of energy for cardiomyocyte
• Fatty acid – 70% of energy supply for the heart, mostly C16 and C18 – mitochondria really like those fatty acids. Fatty acids preferred because about 130 ATP/molecule compared to 36/38 via glucose molecule
• Lactate – 10% of energy use
Numbers shift dramatically during initial burst – glucose would rise to 60-70%, then fall back down as fatty acid transport is increased.
