3 - Mechanisms of Dysrhythmias Flashcards
Intro question: the refractory period of an action potential is related to which ion channel?
Sodium channels
Describe the absolute refractory period
- On the graph, it is the plateau phase (phase 2)
- The cell is NOT ready to accept an impulse
Describe the relative refractory period
- On the graph, it is the phase where the plateau is steadily decreasing (phase 3)
- You won’t normally get an action potential during this time, but if there is a strong enough impulse, there is a possibility the cell will respond
What are the two types of gates in a sodium channel?
- Intracellular plug (intracellular inactivation gate)
- Actual gate (pore region activation gate)
Which gate is open and which gate is closed in a resting cell’s sodium channel
- Intracellular plug (intracellular inactivation gate) is open at rest
- Actual gate (pore region activation gate) is closed at rest
Describe what occurs once an impulse is generated
Once an impulse is generated along the membrane, the pore region opens allowing a rapid influx of sodium and depolarization of the intracellular environment.
After some time, the inactivation gate closes the pore; no more sodium can flow into the cell.
After additional time and change in voltage, the channel recovers to the initial configuration
What does gate closure depend on?
TIME-dependent phenomenon
What does recovery of the sodium channel correspond to?
The absolute refractory period
Describe the absolute refractory period in terms of sodium ion gates
Absolute
- The inactivation gate “plugs” the channel
- This occurs after an action potential
- As time passes, the inactivation gate slowly begins to be removed
Describe the relative refractory period in terms of sodium ion gates
Relative
- When the inactivation gate from the absolute refractory period is slowly being removed, a very strong impulse could alter the inner pore region and an action potential could be generated
- The impulse during this time would have to be very large to get the cell to response
How can channelopathies (genetic channel mutations) and some pharmacological agents affect action potentials?
When mutations or pharm agents affect sodium channels, they can change the kinetics of the channel, which manifests in differences in the refractory period
In addition, this can lead to changes in the flux of other ions and can contribute to arrhythmogenesis
What is excitation-contraction coupling?
The excitation (action potential in the heart cell) leads to the mechanical event (contraction of the heart muscle)
Describe the delay between electrical event and mechanical event in a cardiac muscle cell compared to a skeletal muscle cell
Cardiac = 150 msec. Skeletal = 2-10 msec.
What accounts for this difference?
In cardiac muscle cells, the extended absolute refractory period does not allow another incoming impulse to generate an action potential
Also, cardiac muscle cells (unlike skeletal) cannot be “recruited” when additional force is needed… The electrical events of the heart occur in an “all or non” fashion
What requirement exists for cardiac muscle cell contraction in relation to calcium?
Calcium INFLUX
This is NOT the case for skeletal muscle
Describe the influx of calcium in cardiac muscle cells
In cardiac muscle cells, muscle contraction is dependent upon calcium-induced calcium release
Calcium influx is an absolute requirement for the activation of the calcium-release channels on the SR
Describe the role of calcium in skeletal muscle cells
Calcium influx is not required
- Once stimulated, an end-plate potential can initial skeletal muscle contraction
- Calcium that is released from the sarcoplasmic reticulum in skeletal muscle causes a conformational change in calcium channels, which is the only calcium-related requirement
Describe the “trigger calcium” or “calcium spark” of cardiac muscle cells
The initial calcium influx, which is a required critical step in muscle contraction
Describe how the “trigger calcium” or “calcium spark” is implicated in disease processes
Aging, hypertension, heart failure, diabetes can all lead to…
- Diminished calcium spark
- Reduced contractile potential of the heart muscle
Describe the steps in cardiac muscle cell contraction
1 - Calcium release channels (ryanodine receptors) are activated
2 - Calcium is released into the cytoplasm
3 - Shortening of the muscle occurs as actin filaments interact with the myosin head of thick filaments
4 - Calcium released from intracellular stores bind to troponin protein causing a conformational change
5 - The conformational change uncovers the myosin-binding site on the thin actin filament
6 - Contractile shortening of the sarcomere results
Describe the steps in cardiac muscle cell relaxation
1 - Calcium dissociates from the troponin
2 - Calcium is taken back up into storage via sarcoplasmic reticulum calcium pump (SERCA)
3 - Calcium is bound to proteins within the sarcoplasmic reticulum (SR) in a process involving calsequestrin
4 - Calcium is pumped out of the cell at the cell membrane via the sodium/calcium exchanger (NCX) and the plasma membrane Ca++ pump (plasma Ca-ATPase)
5 - Some believe the mitochondria have a role in calcium cycling
Two types of arrhythmias
1 - Active
2 - Passive
Active arrhythmias
Arrhythmias related to abnormal or enhanced automaticity, triggered activity and reentrant circuits
Automaticity
Automaticity is an intrinsic property of (some) cells of the heart. The sinoatrial (SA) node displays automaticity, as well as cells of the atrioventricular (AV) node, and Purkinje fibers.
SA node
Sinus node is the automatic pace maker of the heart (fastest)
What accounts for the normal physiological automaticity?
This normal, physiological automaticity is due to the phase 4 diastolic depolarization of the action potential in these cells due to the ion flux through the hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel
Which automaticity has the highest slope?
Under normal conditions, the SA node has the fastest rate of diastolic depolarization (highest slope of the phase 4 depolarization) and generates the rhythm that sets the rate for the entire myocardial mass.
What would increasing the slope of phase 4 depolarization result in?
An increased heart rate because if you reach threshold sooner, more action potentials will be possible and the heart rate will therefore be increased
Sinus bradycardia
Sinus bradycardia describes a slower than normal (