Electrophysiology, Excitation, and Contraction Coupling Flashcards
Sequence of Cardiac Electrical Activation
SA Node
Atrium
AV node
Bundle of His
Purkinje Fibers
Ventricles
Which action potentials are similar in the heart, which are unique? SA node, atrium, AV node, Purkinje fibers, ventricle
SA node similar to AV node.
Atrium unique
Ventricle similar to purkinje fibers
Where is this AP taken? What are the phases called? Explain the movement of ions during each of the phases.
Ventricular AP.
Phase 0: Upstroke, Na+ influx
Phase 1: Notch, Na in, K out
Phase 2: Plateau, Ca in, K out
Phase 3: Repolarization, K out
Phase 4: Resting potential, K out, NCX in
What is the resting potential of a ventricular myosite vs an SA node myosite?
-85 mV vs -60 mV
Where is this AP taken? What ion movements are responsible for each phase?
From SA node
Phase 0: Ca influx
Phase 2: Ca in and K out
Phase 3: K out
Phase 4: NCX and If
Differences between SA nodal firing and ventricular firing?
SA nodal firing occurs spontaneously, ventricular firing does not.
Phase 0 is much faster in ventricle!
Phase 1 is absent in SA node
Plateau (phase 2) is subtle and abbreviated in SA node
Phase 3: Same
Phase 4: Voltage increases in SA node and is less negative.
Absolute vs Relative Refractory Period
ARF: Impossible to trigger second AP
RRP: Strong stimuli trigger weak APs.
What is negative current in a whole cell clamp experiment?
Positive charge flowing inward
V=IR
It’s true.
Equilibrium potential of K, Na, Ca
K= -89
Na= +70
Ca= +133
Driving force
DF= V- Equilibrium potential
What happens if V=Ex, V-Ex>0, V-Ex<0?
V=Ex: No ion movement
V-Ex>0: Positive current (cation moves out)
V-Ex<0: Negative current (cation moves in)
What ion does this represent? Why?
Sodium, look at reversal potential around +70.
What ion does this represent?
L-type calcium current, activates and inactivates more slowly than sodium
Role of L-type Ca current in ventricular myocytes
Plateau of action potential, initiate SR calcium release
Role of L-type Ca current in SA and AV nodal myocytes
Action potential upstroke (phase 0)
Why do Calcium channel blockers (Type IV antiarrhythmics, antihypertensives) have multiple bad effects?
Because Ca channels present in many diverse tissues.
Which ion and channel does this represent?
Current through KIR Channel (IK1)
Purpose of KIR
Stabilizes resting potential around ~85mV, also responsible for long plateau when it inactivates
What do these represent?
Delayed rectifier K currents.
Rapid IKr
Slow IKs
Responsible for repolarizing membrane after plateau
Funny Current
IF occurs in SA node, channel is open at very negative voltages, but opens at more positive voltages. Caused by mostly sodium (some K) going in. Supplies depolarizing current to drive voltage upward in SA node.
Where is KIR located?
In ventricle, not in SA node
Why is upstroke (phase 0) so much faster in ventricle?
Because of INa, which is not present in SA node. There, the upstroke is caused by ICa, which is very slow
Which cardiomyosites have delayed rectifier K channels?
SA and ventricle
How do the concentrations of calcium in the SR and cytosol compare?
SR concentration is MUCH higher (10,000x)
CICR
Calcium Induced Calcium Release. Can’t have release of Ca from SR without calcium. Required for contraction.
Steps of EC coupling in cardiac muscle
Excitation is coupled to contraction. First, depolarization causes L-type calcium current. Ca binds to ryanodine receptors in the SR membrane, which releases 4x more calcium, which causes contraction by binding to troponin.
How is such a large concentration of Ca built up in SR?
SERCA, transports Ca in using ATP
NCX
3 Na in along gradient, 1 Ca out against gradient
EC coupling in skeletal muscle
NAChR opening causes influx of sodium, which induces action potential in muscle cell, which causes activation of Ltype Ca channels that are bound directly to ryanodine receptors. NO extracellular CA influx necessary.
How does Ca influx induce contraction in cardiomyocytes if they are so huge?
T tubules (membrane invaginations) extend into cell interior. This way, calcium that surrounds the cell can sit near interior.
T Tubules and RyR location
RyRs sit close to T tubules so calcium doesn’t have to diffuse too far in order to cause CICR.
How does the cardiac myocyte relax after contraction?
70% of calcium is pumped back into SR, 20% pumped out via NCX.
In steady state conditions, total amount of Ca entering through L type Ca current must equal…
Total amount of Ca released via RyRs must equal…
Total amount of Ca exiting via NCX
Total amount resequestered by SERCA
How is strength of contraction modulated?
By altering the amount of Calcium stored in the SR. Also, the effect is nonlinear.
What happens in non-steady state conditions? When does this happen?
Total Ca entering different than total amount exiting. This causes more IC calcium, more in SR. Causes bigger contractions. This happens during exercise.
Can RyRs randomly and spontaneously release Ca?
Yes. Usually these effects are harmless and localized, but it can be bad sometimes!
What happens when multiple RyRs open spontaneously?
High IC calcium can diffuse to other RyRs causing increased opening. This will increase IC Ca some more, and the NCX will have to work harder. This can create a depolarizing current due to the fact that more sodium in brought into the cell, causing inappropriate action potentials.
DAD
Delayed after depolarization. One is okay usually, but more can initiate aberrent action potential.
Cellular correlates of heart failure
Weaker contractions, slower relaxation. Caused by downregulation of SERCA. So, less Ca is pumped into the SR, less released, smaller contractions. Also, disrupted T-tubule structure, which causes increased distance to ryanodine receptors.
Digitalis
Na-K pump inhibitor. Used in heart failure. Inhibition causes increased IC Na, so NCX is less effective. More intracellular Ca, which is pumped into SR. This causes stronger contractions upon release. But can lead to arrhythmias.
Positive Inotropy
Stronger contractions
