111 Impulse Propagation and Pacemaking

Question 1

What is the sarcolemmal Ca2+ clock?

Answer 1

Sarcolemmal Ca2+ clock = Na+/Ca2+ exchanger (1 Ca out/ 3 Na+ in)

Contributes to Phase 4 Depolarization

Activated in response to Ca2+ influx through T-type Ca2+ channels at the end of phase 4, that causes Ca2+ release from the sarcoplasmic reticulum via RyRs

Question 2

What are the 4 mechanisms responsible for automaticity in the pacemaker cells?

Answer 2

1. The I_K responsible for maintaining resting membrane potential graudally decreases. Less K+ leaks out
2. I_f allows Na+ to leak in during phase 4. (+) charge leaks in
3. T-type Ca²⁺ channels are activated as Vm increases toward the end of phase 4 depolarization. Last push to threshold
4. Na⁺/Ca²⁺ exchanger is activated due to the release of Ca²⁺ from the sarcoplsamic reticulum, via RyRs.
   
   • 1 Ca²⁺ out for 3 Na⁺ in = Net inward Na+ current

1-3 = Membrane voltage clock

4 = Sarcolemmal Ca²⁺ clock

Question 3

Electronic conduction of action potentials is decremental.

What does this mean?

Answer 3

The impusle ampliude decreases exponentially with time and distance

Question 4

What is longitudinal resistance (r_i​)?

How does it affect the speed of propagation of an impulse?

Answer 4

Longitudinal resistance (r_i) is intracellular resistance

More resistance –> slower propogation

Question 5

If capacitance is increased, will impulse propagation be slower or faster?

Why?

Answer 5

Increased capacitance = slower propagation

More charge is required to overcome the capacitance and depolarize the cell

Question 6

What is local circuit current?

Answer 6

Flow of current between a depolarized and non-depolarized cell

Question 7

Why are new action potentials required to sustain impulse propagation?

Answer 7

Electronic conduction is decremental (signal decreases as time and distance from the initial impulse increases)

the signal would “run out” of new action potentials were not generated

Question 8

What is membrane resistance (r_m)?

How does it affect the speed of impulse propagation?

Answer 8

Membrane resistance (r_m) is the resistance across a cell membrane

Increasing r_m = faster propgation (less current is lost)

Decreasing r_m = slower propagation

Question 9

Compare the speed of impulse propagation:

Pacemaker cells vs. Cardiomyocytes

Explain

Answer 9

Pacemaker cells have slower conduction and delayed impulse propagation compared to cardiomyocytes.

Pacemaker cells depend on Ca2+ for depolarization, which is slower than the Na+ current that facilitates depolarization in other cells

Question 10

What is the resting potential of the pacemaker cells of the heart?

How does this affect their function?

Answer 10

SA Node: -60 mV

AV Node: -60 mV

Purkinje Fibers: -80 mV

Na+ channels governed by the m and h gates are inhibited at this voltage; the phase 0 upstroke is instead accomplished by the Na+/Ca2+ exchanger that allows 3 Na+ into the cell for every Ca2+ out.

Question 11

What is the space constant, as it relates to impulse propagation?

How is it calculated?

Answer 11

Space constant = the distance from the source at which the amplitude of the impulse is (1/e) * V_o

Depends on r_m and r_i - Calculation shown below

Question 12

List the sequence of propagation of an impulse from the sinus node to the ventricular myocardium

Answer 12

1. SA node
2. 3 inter-nodal pathways
3. AV node
4. Bundle of His
5. Left and Right bundle branches
6. Purkinje fibers -> Ventricular muscle
   
   • From the apex of the heart to the base

Question 13

What feature of adjacent cells allows us to treat them like an “electric cable?”

Answer 13

Gap junctions that contain connexins

Connexing are proteins that contain electrically conduction channels

Question 14

What are connexins?

Answer 14

Proteins in gap junctions between cells that contain electrically conducting channels

They are responsible for propagating impulses from cell to cell

Question 15

What is the resting membrane potential in the Purkinje fibers?

How does this impact their pacemaker function?

Answer 15

Vm = -80 mV

This is too low for T-type Ca2+ activation, so they do not depend on T-Type Ca channels for automaticity

For reference, the 4 mechanisms of automaticity:

1. The I_K responsible for maintaining resting membrane potential graudally decreases. Less K+ leaks out
2. I_f allows Na+ to leak in during phase 4. (+) charge leaks in
3. T-type Ca2+ channels are activated as Vm increases toward the end of phase 4 depolarization. Last push to threshold - Not active in Purkinje
4. Na+/Ca2+ exchanger is activated due to the release of Ca2+ from the sarcoplsamic reticulum, via RyRs.

• Ca2+ out for 3 Na+ in = Net inward Na+ current
• 1-3 = Membrane voltage clock*
• 4 = Sarcolemmal Ca2+ clock*

Question 16

What are M cells in the heart?

How doe they differ from endocardial and epicardial cells?

Answer 16

M cells are cardiomyocytes located in the mid-myocardium

They have less I_K, which increases their action potential duration in comparison to endocardial and epicardial myocytes

The result is that their action potentials are disproportionately prolonged in response to factors that influence action potential duration (cycle length, electrolyte concentration, some drugs)

Question 17

What is the only conduction pathway from the atria to the ventricles?

Answer 17

The AV node

Question 18

In which cells does phase 4 depolarization occur?

Answer 18

Pacemaker cells

(SA node primarily, AV node and Purkinje fibers if necessary)

Question 19

What is the time constant, as it relates to impulse propagation?

Answer 19

Time constant = the time it takes for the the magnitude of the impulse to decrease to (1/e) * V_o

Depends on membrane resistance and capacitance

Calculation shown below

Question 20

What feature of impulse propagation is responsible for the PR interval seen on EKG?

Why is it important?

Answer 20

The PR interval results from slow conduction and delayed impulse propagation due to slow Ca2+ channels in the pacemaker cells

This is imporatant, because it allows the ventricles to fill before they contract