lecture 3 cardiac electrophysiology part i
TRANSCRIPT
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.)