Cardiac Electrophysiology II Flashcards
1
Q
SA Node
A
- normal initiation site of cardiac excitation
- a special characteristic of SA node cells is that they exhibit an intrinsic pacemaker activity
- rate of action potential firing is 60-100/min
- phases 0, 3 and 4
- 0: Rapid depolarization (rising) phase; due mostly to ICa via V-dep, L-type channels
- 3- slower repolarization (falling) phase; due mostly to inactivation of ICa, plus activation of delayed, V-dep IK
2
Q
SA Node Pacemaker Activity
A
- pacemaker activity arises from interaction between ICa (T- type channels), IK, and a special current termed If (different)
- If is the pacemaker current
- If is funny because it is a net inward current that activates in response to hyperpolarization (instead of the usual depolarization) and because it has both an inward (Na) and outward (K) component
- phase 4-slow, ramping depolarization because of the activation of If
- Vagus- ACh opens K hyperpolarizing/ slow down HR
3
Q
Major Calcium Channels in the Heart
A
- L-type: Low threshold (-40mV), slow inactivation (L= long-lasting), large size, SA node pacemaker, atrioventricular conduction, excitation-contraction coupling, contraction of smooth muscle
- T-type: High threshold (-70mV), fast inactivation (transient), small, SA node pacemaker, proliferative signaling
4
Q
Mechanisms to Slow the SA node pacemaker
A
- decreased rate of diastolic hyperpolarization
- diastolic hyperpolarization
- increased threshold
5
Q
ANS regulation of SA Node
A
-pacemaker activity at the SA node is regulated by neuronal input, both parasympathetic inhibition and sympathetic stimulation
-parasympathetic inhibition: the vagal brake
-Vagus nerve (CN X)
-Cholinergic (ACh)
-Muscarinic receptor mechanisms (metabotropic)
-Effect: slows heart/pacemaker rate
Vagal activity -> ACh released at heart at SA node -> ACh binding to, and activation of M2 receptors -> activation of Gi, decrease cAMP
6
Q
Sympathetic stimulation of SA Node
A
- adrenergic receptors (metabotropic): activate Gs -> activate adenylyl cyclase ->increase cAMP -> increase heart rate/ pacemaker rate
- increases phase 4 steepness by increasing inward If and ICaT
- norepi
- threshold lowered due to increase in cAMP
7
Q
Drugs that affect HR
A
- cardioselective beta blockers- block B1-> bradycardia (atenolol, propranolol)
- agents affecting muscarinic ACh receptors- block M2-> tachycardia (atropine)
- nerve agents: inhibit acetylcholinesterase -> bradycardia (Sarin)
- some anti-depressants- block uptake of NE- tachycardia
8
Q
Atrial Muscle AP
A
- Phase 0- Rapid depolarization, due mostly to INa, overshoots OmV
- Phase 1- small, limited repolarization, activation of ITo; decreased ICa and INa
- Phase 2- short plateau of depolarization, ~200 ms; due to prolonged ICa plus a IKur
- Phase 3- repolarization; inactivation of ICa, increased IK
- Phase 4- Resting value of Vm due to increased iKi; no depolarizing ramp
- no If so no intrinsic pacemaker
9
Q
AV Node
A
- AP similar to those of SA node
- AP from SA node arrives in ~30 ms
- have an intrinsic pacemaker activity
- intrinsic rate of AP firing ~40/min
- delayed stage between atria and ventricles (~90 ms)
- Ca upstoke APs like in SA node
- AP magnitude small
- slow upstroke
- high internal resistance of small diameter AV nodal cells
- relatively few gap junctions
- conduction velocity low
- para inhibition- decreasing firing rate; decrease conduction velocity
- symp inhibition- increase firing rate; increase conduction velocity
10
Q
Bundle Branches/ Purkinje Fibers
A
- highest conduction velocity in heart (~4 m/s; ~80X nodes, ~4X muscle)
- AP are similar to muscle cells- but Purkinje fibers have a pacemaker current If
- intrinsic firing rate: <20/min and irregular (tertiary effect)
11
Q
Ventricular Muscle AP
A
- AP similar to those of atrial muscle
- no intrinsic pacemaker activity
- spatiotemporal characteristics of ventricular activation
- ventricular apex (bottom) (endocardium to epicardium) -> ventricular base (top) (endocardium to epicardium)
- Coordinated contraction of ventricular muscle cells that produces very efficient ejection of blood: achieved by a wave of electrical excitation, contraction coupled to electrical excitation, the heart consists of two electrical syncytia
12
Q
Propagation of Cardiac APs
A
- APs potentials propagate from cell to cell by direct electrical coupling via gap junctions
- intracellular channels that permit the passage of ions and small molecules between cels
- consists of 4 or 6 copies of a family of proteins called connexins
- provide the physical basis for the electrical coupling of cardiac cells (contrast this with the chemical neurotransmitter mechanisms of information transfer typically used in the nervous system
13
Q
Summary of electrical activation of the heart
A
- depolarize atria
- depolarize serptum from left to right
- depolarize anteroseptal region of myocardium toward the apex
- depolarize bulk of ventricular myocardium,from endocardium to pericardium
- depolarize posterior portion of base of the left ventricle
- the ventricles are now depolarized
14
Q
Normal activation sequence, conduction velocity, and pacemaker frequency
A
- SA node, <0.01m/s, 60-100 pacemaker discharge
- Atrial myocardium, 1-1.2m/s, no pacemaker
- AV node, 0.02-0.05, 40-55 pacemaker discharge
- AV bundle, 1.2-2.0, 25-40 pacemaker discharge
- Bundle branches, 2.0-4.0 m/s, 25-40 pacemaker
- Purkinje network, 2.0-4.0 m/s, 25-40 pacemaker
- Ventricular myocardium, 0.3-1 m/s, no pacemaker
