Cardiac Electrophysiology II Flashcards
SA Node
- 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
SA Node Pacemaker Activity
- 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
Major Calcium Channels in the Heart
- 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
Mechanisms to Slow the SA node pacemaker
- decreased rate of diastolic hyperpolarization
- diastolic hyperpolarization
- increased threshold
ANS regulation of SA Node
-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
Sympathetic stimulation of SA Node
- 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
Drugs that affect HR
- 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
Atrial Muscle AP
- 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
AV Node
- 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
Bundle Branches/ Purkinje Fibers
- 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)
Ventricular Muscle AP
- 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
Propagation of Cardiac APs
- 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
Summary of electrical activation of the heart
- 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
Normal activation sequence, conduction velocity, and pacemaker frequency
- 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