1. The cardiac electrical system is led by the sinoatrial node which acts as the primary pacemaker at 60 beats per minute. The atrioventricular node and Purkinje fibers can also act as secondary and tertiary pacemakers. 2. There are different types of action potentials in cardiac muscle depending on the region. Sinoatrial and atrioventricular nodes have slow action potentials without phases 1 and 2 due to different ion channel expression compared to ventricular myocytes. 3. Drugs like calcium channel blockers, potassium channel blockers, sodium channel blockers, and beta blockers can be used to pharmacologically manipulate heart rate and conduction velocity by affecting ion channels.

1. Cardiac Electrophysiology Part I Lecture 3

2. Direction of cardiac muscle depolarization

3. Electrical system of the heart Purkinje fibers Bundle of His Sinoatrial node Atrioventricular node 3 possible Pacemakers – Primary – Sinoatrial node, Secondary – Atrioventricular node Tertiary – Purkinje fibers

5. Generic action potential

6. I Na+ rapid depolarizing (non-nodal) I K+ repolarizing (all myocytes) I Ca+ depolarizing (nodal AP and myocyte contraction) I f “ funny channel” or HCN Pacemaker current (activated during hyperpolarization) H yperpolarization activated C yclic N ucleotide gated channel Na + /K + (activated during depolarization) MAJOR MYOCYTE ION CHANNELS Which channel is absent in SA and AV node? Absent in ventricular myocytes? Read- Table 20-1

7. intracellular extracellular (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

8. Ventricular action potential 5 Phases 0 – upstroke of AP I ca+ – slow I ca+/ I na+ - fast 1 – rapid repolarization I k+ – activation I ca+/ I na+ - inactivation 2 – plateau phase I ca+/ I na+ - activated 3 – repolarization I k+ 4 – diastolic potential I k+ I ca+ I f Produce pacemaker activity SA/AV node, purkinje use I f Phase 1 and 2 not present in SA/AV node

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

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

11. Effective and relative refractory periods ERP RRP ERP due to inactivated Na and Ca channels, once they begin to recover the RRP begins.

12. Velocity of electrical conduction Purkinje fibers Bundle of His Sinoatrial node 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?

14. 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

15. Calcium channel blockers Decrease entry of calcium and delay the depolarization of SA and AV nodal cells. Used for: Angina Hypertension Arrhythmias Dihydropyridine class and Verapamil

16. 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).

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

18. Beta blockers -Prevent calcium entry into the cell - Decrease HR, conduction velocity, strength of contraction. -Used to treat many CVS conditions: -Hypertension (inhibit renin) -Angina/myocardial infarction - Arrhythmias (slows rate of depol.)