Cardiac ElectrophysiologyPart I

Lecture 3

Direction of cardiac muscle depolarization

Electrical system of the heart

Purkinje fibers

Bundle of His

Sinoatrialnode

Atrioventricular node

3 possible Pacemakers – Primary – Sinoatrial node, Secondary – Atrioventricular nodeTertiary – Purkinje fibers

Pacemaker activity

• Spontaneous time-dependent depolarization leading to action potentials

• Pacemaker with highest frequency sets the heart rate. – SA node – 60 b/min – smallest electrical region in the heart, sum

of 3 ion channels produces pacemaker (ca, k, f)– AV node – 40 b/min – can take over for SA node, pacemaker

determined by same three channels as SA node. – Purkinje fibers – slow – 20 b/min – unreliable pacemaker, but

great conducting system, pacemaker determined by ‘f’ channels only.

Generic action potential

INa+

rapiddepolarizing(non-nodal)

IK+

repolarizing(all myocytes)

ICa+

depolarizing(nodal AP

and myocytecontraction)

If

“funny channel” or HCNPacemaker current

(activated during hyperpolarization)Hyperpolarization activated Cyclic

Nucleotide gated channel

Na+/K+

(activated during depolarization)

MAJORMYOCYTE

ION CHANNELS

Which channelis absent in SA and AV node?Absent in ventricular myocytes?

Read-Table 20-1

intracellularextracellular(interstitial fluid)

[Na+] 10 mM

[K+] 120mM

[Ca+] .0001 mM

[Na+] 145 mM

[K+] 4.5 mM

[Ca+] 1.0 mM

Intra and extracellular ion concentrations

[A-] protein 4 mM[A-] protein 0 mM

[Cl-] 116 mM [Cl-] 20 mM

Resting membrane potential ~ -(60-80) mV

Ventricular action potential5 Phases

0 – upstroke of APIca+ – slowIca+/Ina+ - fast

1 – rapid repolarizationIk+ – activationIca+/Ina+ - inactivation

2 – plateau phaseIca+/Ina+ - activated

3 – repolarizationIk+

4 – diastolic potential Ik+

Ica+

If

Produce pacemaker activitySA/AV node, purkinje use If

Phase 1 and 2 not present in SA/AV node

Comparison of slow nodal and fast non-nodal cardiac action potentials

Another comparison of slow nodal and fast non-nodal cardiac action potentials

Effective and relative refractory periods

ERP RRP

ERP due to inactivated Na and Ca channels, once they begin to recover the RRP begins.

Velocity of electrical conduction

Purkinje fibers

Bundle of His

Sinoatrialnode

Atrioventricular node

(0.05 m/s)

(0.05 m/s)

(1 m/s)

(1 m/s)

(4 m/s)

Functionally, how might the speeds be important?

1. Decrease RATEof depolarization (more time to reach threshold)

2. Decrease maximum diastolic potential.(more time to reach threshold)

3. Increase threshold potential.(more time to reach threshold)

Decrease in If activity

Increase in Ik activity

Decrease in Ica activity

Parasympathetic vagal release of acetylcholine

Mechanisms for altering heart rate or rate of nodal depolarization

Read about catecholamines p. 493

Pharmacological manipulation of ion channels and heart rate and conduction velocity activity.

Potassium channel blockers – Increase AP duration and ERF (phase 3)Calcium channel blockers – L-type Ca, slows rate in SA and AV node

Sodium channel blockers – Reduce phase 0 and slope of depolarization

Calcium channel blockers

Decrease entry of calcium and delay the depolarization of SA and AV nodal cells.

Used for:Angina

HypertensionArrhythmias

Dihydropyridine class and Verapamil

Potassium channel blockers

-Slow repolarization and therefore extends the Effective Refractory Period. -Extends the “Q-T interval” on the electrocardiogram (lecture Part II)-Helpful in preventing tachyarrhythmias from re-entry mechanisms (lecture Part II).

Sodium channel blockers

-Slow the rate and magnitude of depolarization in non-nodal cells-Used to treat tachycardia-Extends the Effective Refractory Period

Beta blockers

-Prevent calcium entry into the cell -Decrease HR, conduction velocity, strengthof contraction.

-Used to treat many CVS conditions:

-Hypertension (inhibit renin)-Angina/myocardial infarction-Arrhythmias (slows rate of depol.)