Week 04 Lect. 3 - Origin/Spread of Cardiac Excitation Flashcards
What is the volume of cardiac output per minute?
5-6 L/min
What is the mean arterial pressure under resting conditions?
90-95 mmHg
What is the route of cardiac excitation starting from its pacemaker onward?
SA node > AV node > bundle of His > bundle branches (Tawara) > Purkinje fibers + ventricular myocytes
What are the two kinds of APs generated in cardiac tissues and which tissues are they created in?
How do these action potential graphs look?
- Slow Response AP - nodal (SA/AV) cells
- Fast Response AP - atrial/ventricular myocardia
How do the intrinsic pacemaking frequencies of different heart tissues compare?
SA node…
Atrial/Ventricular myocytes…
AV node/bundle of His…
Bundle branches/Purkinje fibers…
SA node: 70-80 bpm
Atrial/Ventricular myocytes: none
AV node/bundle of His: 40-60
Bundle branches/Purkinje fibers: 20-40
What is the current responsible for the “pacemaker potentials” of the heart?
Via what channel + how is it activated?
What ions/which direction?
If (funny) current
- HCN4 channel - activated via hyperpolarization (< -50 mV) and increased cAMP
- Na+ ions diffuse into nodal cells
What is the current responsible for the initial depolarization of the SA node?
Via what channels + how?
What ions + in which direction?
ICa,T or Transient Current (b/c it inactivates)
- T-type VDCC - -55 mV threshold
- Na+ and Ca++ ions diffuse into cell
What is the current responsible for the “depolarization” phase of SA node potentials?
Via what channels + how?
What ions + in which direction?
ICa,L (long-lasting) current
- L-type VDCC - -25 mV threshold
- Ca++ ions diffuse into cell
What is the current responsible for repolarizaton of SA node APs?
Via what channels + how?
What ions + what direction?
Ik current
- Multiple types of K+ channels (Ito, Ikis, Ikr, Ikur)
- K+ ions diffuse out of the cell
What is the current responsible for hyperpolarization of the SA node?
Via what kind of stimulation?
What channels?
What ion + which direction?
IK,ACh Current
- via ACh signals from the vagus nerve
- GIRK1/4 channels
- K+ ions diffuse out of cell
What common drug is used to slow heart rate via the SA node and how?
Ivabradine
- specific inhibition of the “funny” channel slows the prepotential created by If
What common cardiac arrhythmia drug effects the SA node and how?
Verapamil
- blocks the T-type calcium channel affecting the It current of early SA node depolarization
(although Wikipedia says it’s an L-type blocker… lecture slides say T-type)
What is the ion channel associated with funny current (acronym and full name)?
What two ways can it be activated?
HCN - Hyperpolarization-activated cyclic nucleotide-gated ion channel
- hyperpolarization below -50 mV (voltage sensor, subunit 4)
- cAMP binding
How long do the two channels responsible for the majority of depolarization of the SA node remain open?
T-type - 25 ms
L-type - 100 ms
What are the two different ways that parasympathetic innervation can effect heart contraction via two different sites of innervation?
Via what nerve?
Right Vagus > SA node = neg. chronotropic effect
Left Vagus > AV node = neg. dromotropic effect (slows speed of conduction)
- note that vagus does not innervate ventricles
What two aspects of pacemaker potentials are affected by autonomic innervation?
- Minimum Diastolic Potential - lowest Em value during the AP
- Slope of Prepotential - rate of diastolic repolarization via funny current
Describe the mechanism of sympathetic regulation of heart rate…
What is the neurotransmitter, receptor, G protein and effects?
- Norepinephrine
- β1 receptor
-
Gs activation
- increased cAMP
- increased If
- increased ICa,L permeability
Describe the mechanism of parasympathetic regulation of heart rate.
Give the neurotransmitter, receptor, G protein and effects.
- Acetylcholine
- M2 muscarinic receptor
-
Gi (α subunit)
- decreased cAMP
- decreased funny current
- decreased ICa,L current
-
Gi (βγ subunits)
- IACh,K current via GIRK channels causes hyperpolarization
What did the lecture’s example of “pharmacological denervation” of the heart show regarding autonomic control of heart rate?
How?
Parasympathetic innervation has a greater effect on heart rate than sympathetic.
- Using the muscarinic (parasympathetic) blocking agent Atropineraises heart rate much more than using the adrenergic (sympathetic) blocking agentPropranolol lowers it
What happens if SA node pacemaking fails?
Other HCN Channel-containing cells take over
- the cells with the highest endogenous frequency take over
In order of frequency:
- AV node
- Bundle of His
- Tawara Branches
- Purkinje fibers
How does cardiac excitation spread between cells of heart tissues?
via gap junctions
What determines the rate of propagation of APs in the heart?
Strength of the depolarizing current
- higher/faster depolarization = faster conduction
- therefore “slow response” tissues such as the nodes have slower conduction
What causes the fast depolarization seen in “fast response” cardiac tissues?
voltage-gated Na+ channels
In what heart tissues is conduction fastest?
Why?
Bundle of His + Purkinje Fibers
- these cells have a large diameter and thus conduct faster
(they are also “fast response” tissues displaying quicker depolarization phases)
What delays contraction of the atria in comparison to the ventricles?
How?
The AV node is the site of delay
- the connective tissue “fibrous skeleton” of the heart between the atria and ventricles insulates the electrical activity initiated by the SA node
- the AV bundle passing through this insulation has only a few, thin “penetrating fibers” which conduct slowly due to their small diameter
How is the speed of conduction regulated by the two branches of the autonomic nervous system?
What is this effect called?
Dromotropic Effect
Sympathetic: Positive Dromotopic effect
Parasympathetic: Neg. Dromo. effect (Left vagus > AV node)
