20110113 Lecture 10 notes
From Iusmphysiology
- started here on 01/13/2011 at 8AM (not 11AM like the schedule says)
[edit] The Cardiac AP
- Michael Sturek, Ph.D., Professor and Chair
Sturek has many office hours; visit.
- Department of Cellular & Integrative Physiology, MS 385, 274-7772, Email msturek@iupui.edu
- We'll be doing 3 lectures on cardiac AP and ECG.
- Comment on overall approach:
- Dr. Packer gives intro.
- Look at notes before class.
- Readiness questions are to understand what we already know.
- Objectives are oriented toward step 1 boards and are similar to American Physiological Society's objectives.
- The text is good; read it when you need some more information.
- 50% of AP stuff is from the text.
- 80% of ECG stuff is form the text.
[edit] References
- Boron, W.F. and E.L. Boulpaep. (“B&B”) Medical Physiology. Philadelphia: Saunders, 2005.
- Relevant reading –
- B&B, Lederer, Chapter 20, Cardiac Electrophysiology and the Electrocardiogram
- Berne RM and Levy MN. (“B&L”) Physiology. St. Louis, MO: CV Mosby, 1997 (or most recent edition)
- Rhodes, R.A. and Bell, D.R. Medical Physiology: Principles for Clinical Medicine. Baltimore: Lippincott, 2009; Chapter 12.
[edit] Overall Learning Objective
- Understand the electrical signaling system and underlying cellular ionic mechanisms in the heart, which are essential for the coordinated function of pumping blood.
[edit] Specific Learning Objectives
- Know the electrical coupling between cardiac cells and its function.
- Know how excitation spreads from the SA node to other regions of the heart.
- Differentiate the shapes and the durations of action potentials in different regions of the heart.
- Know the 3 physiological functions of cardiac action potentials.
- Understand the ionic mechanisms underlying the different phases of an action potential in a myocardial and pacemaker cells.
- Know the mechanisms of pacemaking by which the rhythm of the heart can be altered.
- Understand the origin and significance of plateau phase of cardiac action potential relevant to the electrical refractoriness of cell.
- Understand how ionic equilibrium potentials contribute to excitation of the heart.
- Know the major ion channel types in myocardial cells.
- Know how intracellular action potentials contribute to integrated extracellular electrical activity, which is the EKG.
[edit] Problem-Based Examples
- Would Dr. Kevorkian use Na or K in his euthanasia cocktail and why?
- K because high extracellular K reduces the potential across the membrane and decreases production of APs, thus stopping heart contraction.
- Why does coronary artery disease, which results in increased extracellular K, slow electrical conduction?
- Higher ECF K concentrations decrease the potential across the membrane, thus ....
- What would be the composition of a cardioplegia solution that you would use to arrest the heart for open-heart surgery?
- Long QT syndrome leading to sudden death – Na and K channel mutations
- "Use-dependent" block of Na channels by anti-arrhythmic drugs (e.g. lidocaine)
- Wolf-Parkinson-White syndrome – AMP kinase mutation leading to glycogen accumulation and accessory conduction pathway
- Mishap in execution by lethal injection in Florida
[edit] Outline
- Introduction and overview, resting, and action potentials
- Ionic basis, ion channels
- Pacemaker potentials
- Cellular heterogeneity (specialization)
- Cellular basis for electrocardiogram (ECG, EKG)
- These notes contain all the information on cardiac electrophysiology and the ECG that is needed for this course.
- Little red flags mean know it!
[edit] Ionic basis, ion channels
[edit] Pacemaker potentials
[edit] Cellular heterogeneity (specialization)
[edit] Cellular basis for electrocardiogram (ECG, EKG)
[edit] Introduction and overview, resting, and action potentials
- Netter has a very nice drawing.
- SA node is where pacemaking starts.
- Automaticity, we'll talk more about it.
- Spontaneous depolarization...more later.
- Fibrous material provides a nice conduction delay to time the atria and ventricles.
- Perkinje fibers:
- Contractile and neuronal, a hybrid.
- These require gap junctions, though, they do not have neuron axons or synapses.
- Duration of ventricular APs can vary:
- This will change the T wave.
- Altered ST and T wave will be what we see in patients.
- Time course ECG:
- Broken down very nicely in the image.
[edit] Conduction of action potential via gap junctions
- B&B, Fig. 9-1
- Intercalated discs
- Desomosomes provide stability
- Gap junctions are permeable to ions.
- This is how ions get from cell to cell to generate syncytium.
- Actin and myosin for contractile apparatus.
- How do you move the AP?
- Via gap junctions
- See animation
- B&B makes this a bit confusing, he'll clarify.
- He deleted the extracellular current flow; just consider depolarizing current through ion channels resulting in depolarization and the current flow through gap junctions.
- There is a net increase in positive charge in the cell.
- This makes the outside relatively negative.
- Depolarization occurs.
- Outside remains relatively negative.
- Gap jxn allows propogation to the next cell and depolarization.
- Not exactly like a nerve.
[edit] Functional syncytium of myocardium requires coupling of cells
[edit] Electrotonic spread of potentials (B&B, Fig. 20-2B)
- There is an eletrotonic spread of the potential along a distance.
- If it is above threshold, (less negative) when it hits the next cell, you will fire another AP and then at C and D etc.
- If not, then that cell will not fire and the AP degrades.
- Here the length constant is important.
- You must have full blown AP to have calcium-induced calcium release and contraction.
- What is threshold?
- There isn't an absolute mV value.
- Depends on the clel and such.
- "When the net inward current is greater than the outward current."
- "When the depolarizing current is greater than the repolarizing current."
- Myelinated nerves have more passive conduction.
- Heart doesn't have myelination, though.
- "Myelinated nerves have more passive conduction; gap junctions and more regenerative action potentials needed in cardiac muscle."
[edit] Resting and action potentials
- We'll look at the easiest cell model: ventricular cell.
- Intracellular electrode is set in the cell and in the ECF to know the transmembrane potential.
- Not performed clinically because we don't have a catheter that can do this and no pt gives cardiac biopsy.
- This cell model gives the AP we've seen before.
- We will see this again next year, too.
- Along the time of an AP:
- Na flows heavily inward.
- Ca flows heavily inward.
- K flows increasingly outward.
- A little Na and Ca influx even at rest.
- AP is 200 to 300 milliseconds.
- 100 to 200 fold longer than the 2 millisecond AP of a nerve.
- How can we have a longer duration of an AP in this cell?
- Ca channels activate more slowly.
- Ca channels stay open longer and offset the K that is effluxing.
- K channels take a little longer to activate.
- There is an electromechanical delay
- Takes a bit of timem for ca-incudce ca-rlease and for the contract apparatus do do their thing.
- Refractory period is important for proper contraction.
- An AP is not necessarily indicative of contraction:
- They can be disconnected.
- Pts can have good ECG but bad contraction.
- Resting membrane potential in neuron is -70 mV.
- Resting membrane potential in cardiac is -93 mV, ish. But we don't need to know an exact value.
- Different texts pick different numbers.
[edit] Nernst equation for ELECTROCHEMICAL equilibrium
- Nernst will be on the boards.
- This equiation combines the electrical and chemical forces over the membrane.
- RT / zf simplifies to 61.54
- What value you use depends on the temperature you put in there.
- Whether you use 60 or 61.54 doesn't produce much difference.
- For cardiac we say that at -91, the chemical and electrical forces balance one another.
- Note that each ion, individually, gives a distinct positive, but they sum to a pretty negative potential.
- Why is this important, clinically?
- Cardiac glycosides: ouabain, digitalis, strophanthidin
- Block Na pump to increase intracellular Na
- Alters the Na equilibrium potential
- Myocardial ischemia can cause increase in ECF potassium
- Affects resting and equilibrium potential
- Affects muscle excitability
- Cardiac glycosides: ouabain, digitalis, strophanthidin
- What do tehse eequilibirum potentials give me?
- Hard to understand them in a table.
- In an ideal square cell:
- High K inside low outside, etc. for all ions.
Got a bit lost. Read slides, understand.
- This is resting vent cell.
**Golden rule: resting membrane will go to ?
- Overshoot will occur.
- "Driving force . force driving Vm toward Eion"
- "Basically, all ion concentrations tend toward equilibrium and the further from equilibrium the greater the force to achieve equilibrium."
- "Vm will go toward Eion if membrane is permeable to the ion (conducts the ion)."
[edit] Ionic basis, ion channels
- Here we see charge over time for ventricular cells
- Na current if fast
- K current is slower
- Gives longer duration AP
- ITO = transient outward current.
- Gives transient bit of tendency to repolarize.
- Ca currents are usally more delayed and long lasting (l type).
- Ca-induced ca release (cicr)
- Question 4: Increased voltage gated Na channels
- Na current is high and gives overshoot.
[edit] Refractory period
- Due to Na channel inactivation
- Step through the animation
- As cell repolarizes, more Na channels ahve gone out of the inactive state and can fire again.
- The number of milliseconds can vary for refractory peiord--it is a fxn of inactivation time of na channels.
- the longer you recover, the more na channels that are ready to activate to provide an enormous overshoot and a normal AP.
[edit] What if you have ECF increases in K?
- In ischemia, Na channels are inactivated and are refractory.
- Seen in hyperkelemia (high K) and bad ischemia which increases K.
Why is K high? Missed some stuff here.
[edit] Pacemakers
- Emphasises phase 4 depolarization.
- Recall that downward is outward flux as a convention in these diagrams.
- See B&B.
- stopped here on 01/12/11 at 9AM.
- started here on 01/14/11 at 11AM.
[edit] Summary of major Currents
- It is pretty well known that
- There are > 20 K channels but we don't need to know them all.
[edit] Cellular heterogeneity
- Syncronization of cells give the mechanical delay that is so important.
- Table:
- We have the different cells, and different currents.
- Main point: if you have b-adrenergic signaling you'll have increased heart rate and increased strengths contractile.
- Main point too: cholinergic is the opposite effect
[edit] Cellular basis for ECG
- Need to understand the basis.
- We will not measure the actual ap in cells in clinic but the ecg gives a good electrical profiling.
- QS = depolarization
- T wave is depolarization
- We generally have 1 second R-R waave which gives 60 beats per minute.
- Most paper is one block per 1 second / 0.2 seconds (by block size).
- U wave is uncommon to see.
[edit] Translating single cell AP to the ECG
- We are giong to think of cellular potentials still, but we will think about two different cells and subtract one from the other.
- Endocardial cell potentials are higher than the epicardial cells.
- Repolarization is from epicardium to endocardium (make sure that's right).
- Quesiton 3: which AP is longer?
- Endocardial AP is longer.
- Endocardia AP is green, epicardial is blue.
- We want to get the subtracted intracellular voltage to translate AP in cells to an ECG.
- On the red line, 1, 2, 3, 4, 5 translates to the QRS and T.
- Now for repolarization phase
- If endo and epi repolar. were the same, you would have a negative T wave.
- Because they are off-set, we see a positive spike (puke colored line in graphs).
- This is the normal scenario.
- Now remember that an ECG is an extracellular recording
- This means we're getting electircal activity, not membrane potentials.
[edit] Extracellular action potentials
- We start off measuring B and A with extracellular leads.
- These are said to be on a lead axis of zero.
- As we depolarize, the inside of A becomes positive and B becomes negative inside.
- This causes the positive deflection on the readout.
- The neg probe will have neg charge around it and positive will have positive.
- With a lead axis of 180 degrees.
- Then the positive node is in a negative field and vice versa.
- This will cuase the exact opposite read out.
- So, the point is that where you put the leads is important.
- Note that all these exmaples will use depolarization from cell a to cell b.
- Lead axis of 90s:
- Here the nodes won't measure any change.
- This is called an isoelectric lead.
- Good for finding the isoelectric lead.
[edit] Problem-based examples
- K for heart:
- Will stop but only after ventricular fibrilation.
- Why did it speed up first?
- Concentration was such that SA node polarized more which increased SA node which increased pacemaking.
- But then, with high concentrations....
- You need to use a barbituate first. In Florida, they forgot the barbituate.
- How do you change membrane potential?
- Can be done by increasing K current to slow AP.
- Could also increase sympathetic innervation (beta adrenergic receptor).
- Could also decrease Ca current.
- Epi and NE would increase IF and decrease K which would be the opposite of Ach.
- Tomorrow will be ECG plus some wrap up from today.
[edit] Other currents
- Yes, other currents matter.
- Even Ca+ channels matter, too.
- continued on to F513 ECG I II print v7.pptx on 01/14/2011