Lectures 26 & 27: Cardiac Electrophysiology Flashcards
Types of cardiac action potentials
- Fast response
- Slow response
Fast response type cardiac APs
- Contracting fibers
- Fast conducting tissue (like the Purkinje fibers)
- NOT nodal cells
Slow response type cardiac APs
- SA node
AV node - Remaining conducting fibers
Phases of the fast response AP
- Phase 0 = upstroke
- Phase 1
- Phase 2
- Phase 3
- Phase 4
Phase 0/upstroke
- Fast response action potentials are generated in cells that have fast sodium channels
- Activation gates open quickly
- Voltage declines rapidly in myocardial cells (even faster in Purkinje fibers)
- As membrane depolarizes, Na inactivation gates start to close
Absolute refractory period (phase 0)
- Voltage dependence of the inactivation gate
- If membrane depolarized more positive than -55 mV, the
cell membranes are inexcitable due to voltage inactivation
Overshoot
- End of phase 0
- Membrane depolarization beyond 0 mV
Also beginning during phase 0
- Activation of slow calcium channels
- Reduction of potassium conductance below resting levels
- Effects manifest during phase 2
Phase 1
- Rapid repolarization
- Activation of transient outward current ito
- Due to opening of a specific K+ channel (4-aminopyridine blocks this K+ channel)
- Prominent in Purkinje and certain ventricular epicardial fibers
Phase 2
- Two nearly balanced ion conductances
- Plateau region of the AP
L-type calcium channel activation (phase 2)
- Membrane reaches about -30 to -40 mV (during upstroke/phase 0)
- Voltage-dependent calcium conductance is activated
- Slow type channel (activated slowly)
Effects of the reduced potassium conductance are seen (phase 2)
- As membrane depolarizes during phase 0
- With depolarization NDF causing outward potassium movement increases
- Causes more K+ ions to leave than Ca2+ to enter
To keep the potential relatively constant for the plateau period (phase 2)
- Potassium conductance must be reduced during the plateau phase
Three channels carrying potassium during the plateau (phase 2)
- ito (not completely inactivated yet from phase 1)
- iK
- iK1
Inward Ca2+ ionic current together with the reduced outward K+ conductance during phase 2
- Maintains membrane depolarized around 0 mV for about 200 msec
Towards the end of phase 2
- Slow Ca2+ channel starts to inactivate
- K+ conductance (iK and iK1) that repolarizes starts to increase
- Accelerates repolarization process
Phase 3 channel activity
- Slow Ca2+ channel is rapidly inactivating
- K+ channel conductance increases (enhancing the outward ionic flux of K+)
- Rapidly repolarizes the fiber (same three potassium channels as in plateau are involved)
- Occurs when K efflux exceeds calcium influx
Phase 4 is flat in
- Ventricular working fibers
- Atrial working fibers
In Purkinje fibers and in SA and AV node fibers (phase 4)
- Maximal Diastolic Potential
- The most negative potential achieved at the end of repolarization
- Followed by diastolic depolarization
Slow response fibers of cardiac APs channel activity
- Slow inward Na+/Ca2+ channels (similar to channels responsible for plateau)
- Fast response action potential in Purkinje fibers can be converted into slow response type by exposure to TTX
The fast Na+ channels become fully activated when
- Vm reaches and declines beyond a threshold value of about -65 mV
- Channel activation sets into motion slower processes that will result in the inactivation of the Na+ channels
When the resting potential is artificially held constant at -70 mV
- About 50% of the fast Na+ channels become inactivated
- In a normal action potential all the fast Na+ channels remain inactivated (voltage inactivation) until the membrane repolarizes to potentials more negative than -55 mV
During the absolute refractory period
- All fast Na+ channels are inactivated
- No matter how great the stimulus applied to a cardiac muscle cell, you cannot elicit another AP
Relative refractory period
- As a cell repolarizes from -55mV to the resting potential, more voltage dependent channels become available
- Becomes possible to elicit an action potential
- However, amplitude of the upstroke is initially small, increasing as the cell repolarizes
- Stimulus intensity required to elicit an action potential progressively declines until it equals the intensity required in a quiescent cell
- Full repolarization marks the end of this period
Refractory period of atrial muscle
- Much shorter than that of ventricles
- So atria can contract at much faster rate than ventricles
In slow response heart fibers, such as the SA and AV nodes, the absolute refractory period
- Extends well beyond Phase 3
The relative refractory period then extends into Phase 4
- Vm is nearly constant
- Slope is slightly rising due to diastolic depolarization
Impulses arriving at a slow response fiber early in its relative refractory period
- Conducted much more slowly than those arriving late in the period
- Thus, the greater tendency for conduction blocks in these fibers
The adult heart normally contracts at a rhythmic rate of
- 70 beats per minute
- Does so in a coordinated manner
- Coordination is provided in two ways
Two ways coordination is provided in heart conduction
- Gap junctions allow spread of AP from one fiber to another
- Specialized conducting system facilitates the rapid and coordinated spread of excitation
Origin of the heart beat
- SA node
Some muscle cells in SA node are autorhythmic
- Capable of spontaneous rhythmical self-excitation
SA node
- Found in posterior wall of the right atrium
- Small strip of specialized muscle
- Initiates the cardiac beat
- Nodal cells are also continuous with the atrial fibers but are not contractile
Characteristics of SA nodal cells
- Vm more positive (-55mV to –65mV) than surrounding contractile atrial cells
- Do not have a steep phase 0
- Do not have phase 1
- Do not have a flat phase 4
- High Na+ conductance (gNa) means Na leaks into cells (causes Vm to be constantly in a state of being depolarized toward threshold during phase 4)
Diastolic depolarization
- Vm constantly in a state of being depolarized toward threshold during phase 4
- A slow response action potential is fired
Each time the ‘resting’ membrane potential is re-established during phase 3
- It gradually decays (diastolic depolarization) until threshold is reached
- AP is fired
- After it is over gK is high and a repolarization occurs (π)
- As the, K+ conductance deteriorates the high gNa causes another gradual depolarization until threshold is reached
With the generation of the rhythmic impulse in the SA node, the impulse spreads to
- Rest of the atrial muscle
- Via the gap junction between atrial fibers themselves
Contraction of the atrium results in
- Forcing blood through the AV valves into the ventricles
Three tracts that convey cardiac impulses directly from SA to AV node are a mixture of
- Ordinary myocardial cells
- Specialized conducting fibers
The cardiac impulse does not travel into the ventricles too rapidly; time is allowed for
- Atria to empty their contents into the ventricles before ventricular contraction begins
AV node delay
- The AV node and its associated conductive fibers delay the transmission
The node and its special fibers are the only
- Electrical connections of the atrium to the ventricles
The impulse reaches the AV node about
- 40 msec after it is initiated
- 110 msec to get out of the node
About one-half of AV time lapse occurs in
- Junctional fibers
- Low conduction velocity
AV node delay (time lapse)
- One-half occurs in the junctional fibers (low conduction velocity)
- Second delay in nodal fibers
- Further delay in transitional fibers and finally into the AV bundle
Purkinje fibers run from
- Fibers from AV node through the bundle of His into the ventricles
Purkinje fibers size
- Large diameter
- High conduction velocity
- Immediate transmission of the cardiac impulse throughout the entire ventricular system
Puekinje fibers travel between
- Valves of the heart into the ventricular septum
- Divide into right and left branches
Purkinje fiber branches
- Each spreads down to the apex of each ventricle
- Then curves back around the lateral wall
Purkinje fiber impulses travel (speed)
- 60 msec from the AV node to all the ventricular fibers
- Thus, ventricle fibers contract at essentially the same time
Primary pacemaker
- The SA node
Ectopic foci
- Other parts of the heart can exhibit rhythmic contractions
- Although, cardiac impulse normally arises in the SA node (primary pacemaker)
Secondary pacemaker
- AV node
- Rate of 40-60 beats/ min
Tertiary pacemaker
- Purkinje fibers
- Discharge at 15-40 beats/min
Overdrive suppression
- Since the SA node has a greater rate, it controls the beat of the entire heart (via overdrive suppression) and is the normal pacemaker of the heart
Rhythmic discharge rate
- Occasionally developed by other parts of the heart as the AV node or Purkinje fibers
- A pacemaker elsewhere than the SA node is an ectopic pacemaker
- Leads to an abnormal sequence of contraction
Ectopic beat
- An abnormal beat that results from a spurious impulse of the cardiac muscle
- Occurs during the non-refractory period
Autonomic control of heart
- Parasympathetics via Vagus (CN X)
- Stimulation causes acetylcholine release
Stimulation of acetylcholine release causes
- Decrease in rate of rhythm of the SA node
- Decreased excitability of AV junctional fibers (slows transmission of cardiac impulses to the ventricles)
Ventricular escape
- Very strong vagal stimulation can stop ventricular beating for 4-10 seconds
- Purkinje fibers will develop a rhythm of their own
- Cause ventricular contraction at 15-40 beats/min
Acetylcholine acts by
- Reducing membrane conductance to Ca2+ and Na+
- Increasing it to K+
- This hyperpolarizes the cell membrane
- Slows down the diastolic depolarization
- Thus, more Na+/Ca2+ must enter before depolarization is sufficient to reach threshold
The level of parasympathetic nerve stimulation will determine
- If the effect is a delay or a blockage of action potential conduction
Sympathetic heart stimulation
- Releases norepinephrine
- Increase rate of SA node discharge
- Increase excitability of all parts of the heart
- Increases the force of contraction
- Increases the conduction velocity from the atria to the ventricles
Sympathetics increase Na+/Ca2+ conductance and
- Accelerates the onset of self-excitation
- Increases heart rate
