Harrison: principles of electrophysiology Flashcards
pathway of cardiac impulse
Pacemaker cells in SA node generate impulse –> atria –> AV node–> bundle of His –> L and R BB –> purkinje –> activation of ventricles
What is the only connection between the atria and ventricles?
AV node
cardiac action potnetial time vs. skeletal muscle cell AP time
Cardiac myocyte action potential time >> skeletal muscle cells
Cardiac: 200-400 ms
Skeletal: 1-5 ms
Think of ventricular AP vs. Atrial AP. Describe difference in the AP curve, and associated channels
Most common ion channel in the heart
voltage gated
Four homogenous subunits (e.g. K channels) or four internally homologous domains (Na and Ca channels)
What is responsible for opening the channel in response to depolarization?
S4- 4th transmembrane segment in the voltage-dependent ion channels
Cardiac arrhythmias result from abnormalities of _____
electrical impulse generation, conduction, or both
What distrubances usually cause bradyarrhythmias?
- impulse formation at level of SA node
- impulse propagation at any level: exit block from sinus node, conduction block in AV node
- impaired conduction in His-Purkinje system
Different mechanisms for Tachyarrhythmias
- Enhanced automaticity (spontaneous depolarization)
- Reentry (circus propagation)
- Triggered arrhythmias (initiated by afterdepolarizations, occur during or immediately after cardiac repolarization, phase 3 or 4 of AP)
Mechanism of ANS on rate of phase 4 depolarization
- PNS: negative chronotropic effect
- release of Ach
- binds Muscarinic receptors
- activate IKACh in nodal and atrial cells
- increases K+ conductance, opposes depolarization, slowing rate of rise of phase 4 AP
- SNS:
- catecholamine release
- activate α– and β–adrenergic receptors
- β1: predominates in pacemaking cells
- both L-type Ca current (ICa-L) and If
- increases the slope of phase 4
Hypokalemia - effect on action potential
- reduces activity of Na/K-ATPase
- Lower potassium levels in the extracellular space
- cause hyperpolarization of the resting membrane potential due to altered K+ gradient
- greater than normal stimulus is required for depolarization of the membrane to initiate an action potential
- reduces repolarizing current
- enhance phase 4 diastolic depolarization
- increase in spontaneous firing
Definition of afterdepolarization, EAD vs. DAD, and difference in mechanisms
Afterdepolarization: spontaneous depolarization
EADs: occur before end of AP (phase 2 and 3)
- enhance of L-type Ca current, inward current
- prolongs AP
- intracellular Ca loading may enhance chance of DAD
DAD: occur during phase 4 after repolarization completion
- increase Ca load in cyotosol and SR
- digitalis glycoside toxicity, catecholamines, and ischemia and nehance Ca loading
Why are pts with ischemia or CHF likely to develop arrhythmias, especially on exposure to AP-prolonging drugs?
- messes with intracellular [Ca2+]
- calcium loading can lead to EADs and DADs
What conditions can predispose generation of EADs and why?
Any condition causing a prolonged AP and QT
-hypokalemia, hypomagnesemia, bradycardia, and drugs (Antiarrhythmics with class IA and III action)
Explain the paradox: decreased [K+]o may decrease membrane potassium currents in the ventricular myocyte
- the reduced extracellular potassium (paradoxically) inhibits the delayed rectifier current IKr
- delays ventricular repolarization
- may promote reentrant arrhythmias,
