Week 04 Lect. 3 - Origin/Spread of Cardiac Excitation

Question 1

What is the volume of cardiac output per minute?

Answer 1

5-6 L/min

Question 2

What is the mean arterial pressure under resting conditions?

Answer 2

90-95 mmHg

Question 3

What is the route of cardiac excitation starting from its pacemaker onward?

Answer 3

SA node > AV node > bundle of His > bundle branches (Tawara) > Purkinje fibers + ventricular myocytes

Question 4

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?

Answer 4

1. Slow Response AP - nodal (SA/AV) cells
2. Fast Response AP - atrial/ventricular myocardia

Question 5

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…

Answer 5

SA node: 70-80 bpm

Atrial/Ventricular myocytes: none

AV node/bundle of His: 40-60

Bundle branches/Purkinje fibers: 20-40

Question 6

What is the current responsible for the “pacemaker potentials” of the heart?

Via what channel + how is it activated?

What ions/which direction?

Answer 6

I_f (funny) current

• HCN4 channel - activated via hyperpolarization (< -50 mV) and increased cAMP
• Na+ ions diffuse into nodal cells

Question 7

What is the current responsible for the initial depolarization of the SA node?

Via what channels + how?

What ions + in which direction?

Answer 7

I_Ca,T or Transient Current (b/c it inactivates)

• T-type VDCC - -55 mV threshold
• Na⁺ and Ca⁺⁺ ions diffuse into cell

Question 8

What is the current responsible for the “depolarization” phase of SA node potentials?

Via what channels + how?

What ions + in which direction?

Answer 8

I_Ca,L (long-lasting) current

• L-type VDCC - -25 mV threshold
• Ca++ ions diffuse into cell

Question 9

What is the current responsible for repolarizaton of SA node APs?

Via what channels + how?

What ions + what direction?

Answer 9

I_k current

• Multiple types of K+ channels (I_to, I_kis, I_kr, I_kur)
• K⁺ ions diffuse out of the cell

Question 10

What is the current responsible for hyperpolarization of the SA node?

Via what kind of stimulation?

What channels?

What ion + which direction?

Answer 10

I_K,ACh Current

• via ACh signals from the vagus nerve
• GIRK1/4 channels
• K⁺ ions diffuse out of cell

Question 11

What common drug is used to slow heart rate via the SA node and how?

Answer 11

Ivabradine

• specific inhibition of the “funny” channel slows the prepotential created by I_f

Question 12

What common cardiac arrhythmia drug effects the SA node and how?

Answer 12

Verapamil

• blocks the T-type calcium channel affecting the I_t current of early SA node depolarization

(although Wikipedia says it’s an L-type blocker… lecture slides say T-type)

Question 13

What is the ion channel associated with funny current (acronym and full name)?

What two ways can it be activated?

Answer 13

HCN - Hyperpolarization-activated cyclic nucleotide-gated ion channel

1. hyperpolarization below -50 mV (voltage sensor, subunit 4)
2. cAMP binding

Question 14

How long do the two channels responsible for the majority of depolarization of the SA node remain open?

Answer 14

T-type - 25 ms

L-type - 100 ms

Question 15

What are the two different ways that parasympathetic innervation can effect heart contraction via two different sites of innervation?

Via what nerve?

Answer 15

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

Question 16

What two aspects of pacemaker potentials are affected by autonomic innervation?

Answer 16

1. Minimum Diastolic Potential - lowest Em value during the AP
2. Slope of Prepotential - rate of diastolic repolarization via funny current

Question 17

Describe the mechanism of sympathetic regulation of heart rate…

What is the neurotransmitter, receptor, G protein and effects?

Answer 17

• Norepinephrine
• β1 receptor
• G_s activation
  
  • ​increased cAMP
  • increased I_f
  • increased I_Ca,L permeability

Question 18

Describe the mechanism of parasympathetic regulation of heart rate.

Give the neurotransmitter, receptor, G protein and effects.

Answer 18

• Acetylcholine
• M2 muscarinic receptor
• Gi (α subunit)
  
  • decreased cAMP
  • decreased funny current
  • decreased I_Ca,L current
• Gi (βγ subunits)
  
  • ​I_ACh,K current via GIRK channels causes hyperpolarization

Question 19

What did the lecture’s example of “pharmacological denervation” of the heart show regarding autonomic control of heart rate?

How?

Answer 19

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

Question 20

What happens if SA node pacemaking fails?

Answer 20

Other HCN Channel-containing cells take over

• the cells with the highest endogenous frequency take over

In order of frequency:

1. AV node
2. Bundle of His
3. Tawara Branches
4. Purkinje fibers

Question 21

How does cardiac excitation spread between cells of heart tissues?

Answer 21

via gap junctions

Question 22

What determines the rate of propagation of APs in the heart?

Answer 22

Strength of the depolarizing current

• higher/faster depolarization = faster conduction
• therefore “slow response” tissues such as the nodes have slower conduction

Question 23

What causes the fast depolarization seen in “fast response” cardiac tissues?

Answer 23

voltage-gated Na⁺ channels

Question 24

In what heart tissues is conduction fastest?

Why?

Answer 24

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)

Question 25

What delays contraction of the atria in comparison to the ventricles? How?

Answer 25

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

Question 26

How is the speed of conduction regulated by the two branches of the autonomic nervous system? What is this effect called?

Answer 26

**Dromotropic Effect** ## Footnote Sympathetic: Positive Dromotopic effect Parasympathetic: Neg. Dromo. effect (_Left vagus \> AV node_)