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Atrial Fibrillation: The Science behind Its Defiance

View Article: PubMed Central - PubMed

ABSTRACT

Atrial fibrillation (AF) is the most prevalent arrhythmia in the world, due both to its tenacious treatment resistance, and to the tremendous number of risk factors that set the stage for the atria to fibrillate. Cardiopulmonary, behavioral, and psychological risk factors generate electrical and structural alterations of the atria that promote reentry and wavebreak. These culminate in fibrillation once atrial ectopic beats set the arrhythmia process in motion. There is growing evidence that chronic stress can physically alter the emotion centers of the limbic system, changing their input to the hypothalamic-limbic-autonomic network that regulates autonomic outflow. This leads to imbalance of the parasympathetic and sympathetic nervous systems, most often in favor of sympathetic overactivation. Autonomic imbalance acts as a driving force behind the atrial ectopy and reentry that promote AF. Careful study of AF pathophysiology can illuminate the means that enable AF to elude both pharmacological control and surgical cure, by revealing ways in which antiarrhythmic drugs and surgical and ablation procedures may paradoxically promote fibrillation. Understanding AF pathophysiology can also help clarify the mechanisms by which emerging modalities aiming to correct autonomic imbalance, such as renal sympathetic denervation, may offer potential to better control this arrhythmia. Finally, growing evidence supports lifestyle modification approaches as adjuncts to improve AF control.

No MeSH data available.


Related in: MedlinePlus

Sinoatrial Node Depolarization. Under normal conditions, the heart’s electrical rhythm is generated by the cells of the sinoatrial (SA) node. At the beginning of each cardiac cycle the membrane potential of the SA cells is approximately -60 mV, with the interior of the SA cells negatively charged relative to the cell exterior. Unlike contractile cardiac cells, SA cells do not have a stable resting membrane potential, so they remain poised at -60 for just the briefest moment, because “funny channels” (If) promptly spring open, allowing positively charged ions to leak from the extracellular space into the interior of the SA cells. As positive ions enter, the SA cell interiors become progressively less negatively charged (depolarized). The funny channel leak current (soon joined by Ca2+ current through T- and L-type channels, ICa(T), ICa(L)) -- and the change in the membrane potential that results from it -- is represented in the graph of the SA node action potential as the diagonal upslope at the start of action potential waveform, also referred to as “phase 4.” The positive ion influx quickly brings the SA cells toward the “threshold potential,” at approximately -40 mV, at which point voltage-gated calcium channels suddenly open, enabling a sudden massive surge of positive charge entry into the cell. This is the upstroke of the SA action potential, also called “phase 0.” Following the upstroke, there is an exodus of positively-charged potassium ions (IK) which restores the cell interior to its original negatively-charged baseline electrical potential during phase 3 repolarization.
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F2-ad-7-5-635: Sinoatrial Node Depolarization. Under normal conditions, the heart’s electrical rhythm is generated by the cells of the sinoatrial (SA) node. At the beginning of each cardiac cycle the membrane potential of the SA cells is approximately -60 mV, with the interior of the SA cells negatively charged relative to the cell exterior. Unlike contractile cardiac cells, SA cells do not have a stable resting membrane potential, so they remain poised at -60 for just the briefest moment, because “funny channels” (If) promptly spring open, allowing positively charged ions to leak from the extracellular space into the interior of the SA cells. As positive ions enter, the SA cell interiors become progressively less negatively charged (depolarized). The funny channel leak current (soon joined by Ca2+ current through T- and L-type channels, ICa(T), ICa(L)) -- and the change in the membrane potential that results from it -- is represented in the graph of the SA node action potential as the diagonal upslope at the start of action potential waveform, also referred to as “phase 4.” The positive ion influx quickly brings the SA cells toward the “threshold potential,” at approximately -40 mV, at which point voltage-gated calcium channels suddenly open, enabling a sudden massive surge of positive charge entry into the cell. This is the upstroke of the SA action potential, also called “phase 0.” Following the upstroke, there is an exodus of positively-charged potassium ions (IK) which restores the cell interior to its original negatively-charged baseline electrical potential during phase 3 repolarization.

Mentions: In contracting atrial cells the very substantial IK1 current, which largely determines the resting membrane potential, swamps out the effects of the funny current leak channels, so that atrial cells do not normally display automaticity [2]. (Fig. 1) The SA node, unencumbered by IK1, initiates each cardiac cycle by self-depolarizing and then passing the depolarization wave to the remainder of the atrial cells [63, 68, 69]. (Fig. 2)


Atrial Fibrillation: The Science behind Its Defiance
Sinoatrial Node Depolarization. Under normal conditions, the heart’s electrical rhythm is generated by the cells of the sinoatrial (SA) node. At the beginning of each cardiac cycle the membrane potential of the SA cells is approximately -60 mV, with the interior of the SA cells negatively charged relative to the cell exterior. Unlike contractile cardiac cells, SA cells do not have a stable resting membrane potential, so they remain poised at -60 for just the briefest moment, because “funny channels” (If) promptly spring open, allowing positively charged ions to leak from the extracellular space into the interior of the SA cells. As positive ions enter, the SA cell interiors become progressively less negatively charged (depolarized). The funny channel leak current (soon joined by Ca2+ current through T- and L-type channels, ICa(T), ICa(L)) -- and the change in the membrane potential that results from it -- is represented in the graph of the SA node action potential as the diagonal upslope at the start of action potential waveform, also referred to as “phase 4.” The positive ion influx quickly brings the SA cells toward the “threshold potential,” at approximately -40 mV, at which point voltage-gated calcium channels suddenly open, enabling a sudden massive surge of positive charge entry into the cell. This is the upstroke of the SA action potential, also called “phase 0.” Following the upstroke, there is an exodus of positively-charged potassium ions (IK) which restores the cell interior to its original negatively-charged baseline electrical potential during phase 3 repolarization.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036958&req=5

F2-ad-7-5-635: Sinoatrial Node Depolarization. Under normal conditions, the heart’s electrical rhythm is generated by the cells of the sinoatrial (SA) node. At the beginning of each cardiac cycle the membrane potential of the SA cells is approximately -60 mV, with the interior of the SA cells negatively charged relative to the cell exterior. Unlike contractile cardiac cells, SA cells do not have a stable resting membrane potential, so they remain poised at -60 for just the briefest moment, because “funny channels” (If) promptly spring open, allowing positively charged ions to leak from the extracellular space into the interior of the SA cells. As positive ions enter, the SA cell interiors become progressively less negatively charged (depolarized). The funny channel leak current (soon joined by Ca2+ current through T- and L-type channels, ICa(T), ICa(L)) -- and the change in the membrane potential that results from it -- is represented in the graph of the SA node action potential as the diagonal upslope at the start of action potential waveform, also referred to as “phase 4.” The positive ion influx quickly brings the SA cells toward the “threshold potential,” at approximately -40 mV, at which point voltage-gated calcium channels suddenly open, enabling a sudden massive surge of positive charge entry into the cell. This is the upstroke of the SA action potential, also called “phase 0.” Following the upstroke, there is an exodus of positively-charged potassium ions (IK) which restores the cell interior to its original negatively-charged baseline electrical potential during phase 3 repolarization.
Mentions: In contracting atrial cells the very substantial IK1 current, which largely determines the resting membrane potential, swamps out the effects of the funny current leak channels, so that atrial cells do not normally display automaticity [2]. (Fig. 1) The SA node, unencumbered by IK1, initiates each cardiac cycle by self-depolarizing and then passing the depolarization wave to the remainder of the atrial cells [63, 68, 69]. (Fig. 2)

View Article: PubMed Central - PubMed

ABSTRACT

Atrial fibrillation (AF) is the most prevalent arrhythmia in the world, due both to its tenacious treatment resistance, and to the tremendous number of risk factors that set the stage for the atria to fibrillate. Cardiopulmonary, behavioral, and psychological risk factors generate electrical and structural alterations of the atria that promote reentry and wavebreak. These culminate in fibrillation once atrial ectopic beats set the arrhythmia process in motion. There is growing evidence that chronic stress can physically alter the emotion centers of the limbic system, changing their input to the hypothalamic-limbic-autonomic network that regulates autonomic outflow. This leads to imbalance of the parasympathetic and sympathetic nervous systems, most often in favor of sympathetic overactivation. Autonomic imbalance acts as a driving force behind the atrial ectopy and reentry that promote AF. Careful study of AF pathophysiology can illuminate the means that enable AF to elude both pharmacological control and surgical cure, by revealing ways in which antiarrhythmic drugs and surgical and ablation procedures may paradoxically promote fibrillation. Understanding AF pathophysiology can also help clarify the mechanisms by which emerging modalities aiming to correct autonomic imbalance, such as renal sympathetic denervation, may offer potential to better control this arrhythmia. Finally, growing evidence supports lifestyle modification approaches as adjuncts to improve AF control.

No MeSH data available.


Related in: MedlinePlus