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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

Atrial Action Potential Ion Currents. While the SA cells are depolarizing, the surrounding contractile cells of the atria are at their resting membrane potential of approximately -90mV, due to the IK1 current. Once the SA depolarizes, it promptly passes depolarizing positive ions to the atrial cells through low resistance gap junction channels. These positive ions bring the atrial cells to their own threshold potential, opening voltage-gated sodium channels (INa) in the atrial cell membranes, so that the atrial cells fire their own action potentials. At the peak of the upstroke in the atria, transient outward (Ito) potassium channels open; positively-charged potassium ions exit the cell, beginning the process of repolarization. Their attempt to repolarize the atrial cells is short-lived however, because inward calcium current, conducted through voltage-gated L-type calcium channels (Ica(L)) keeps the cells in a state of depolarization just a bit longer, depicted as a plateau in the middle of the action potential waveform. The SA action potential does not need a calcium-based plateau current because SA cells are not responsible for contracting. Atrial cells, on the other hand, use the electrical depolarization from the action potential as the signal to contract. The “trigger” calcium entry through L-type channels during the plateau acts as a bridge between the electrical depolarization and mechanical contraction. The L-type channels inactivate rapidly, calcium current ceases, and then potassium exit, through multiple channels including the “ultra-rapid”-opening IKur, the “rapid” opening IKr (also called hERG channels) and the “slowly” opening IKs channels, fully repolarizes the cells.
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F1-ad-7-5-635: Atrial Action Potential Ion Currents. While the SA cells are depolarizing, the surrounding contractile cells of the atria are at their resting membrane potential of approximately -90mV, due to the IK1 current. Once the SA depolarizes, it promptly passes depolarizing positive ions to the atrial cells through low resistance gap junction channels. These positive ions bring the atrial cells to their own threshold potential, opening voltage-gated sodium channels (INa) in the atrial cell membranes, so that the atrial cells fire their own action potentials. At the peak of the upstroke in the atria, transient outward (Ito) potassium channels open; positively-charged potassium ions exit the cell, beginning the process of repolarization. Their attempt to repolarize the atrial cells is short-lived however, because inward calcium current, conducted through voltage-gated L-type calcium channels (Ica(L)) keeps the cells in a state of depolarization just a bit longer, depicted as a plateau in the middle of the action potential waveform. The SA action potential does not need a calcium-based plateau current because SA cells are not responsible for contracting. Atrial cells, on the other hand, use the electrical depolarization from the action potential as the signal to contract. The “trigger” calcium entry through L-type channels during the plateau acts as a bridge between the electrical depolarization and mechanical contraction. The L-type channels inactivate rapidly, calcium current ceases, and then potassium exit, through multiple channels including the “ultra-rapid”-opening IKur, the “rapid” opening IKr (also called hERG channels) and the “slowly” opening IKs channels, fully repolarizes the cells.

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
Atrial Action Potential Ion Currents. While the SA cells are depolarizing, the surrounding contractile cells of the atria are at their resting membrane potential of approximately -90mV, due to the IK1 current. Once the SA depolarizes, it promptly passes depolarizing positive ions to the atrial cells through low resistance gap junction channels. These positive ions bring the atrial cells to their own threshold potential, opening voltage-gated sodium channels (INa) in the atrial cell membranes, so that the atrial cells fire their own action potentials. At the peak of the upstroke in the atria, transient outward (Ito) potassium channels open; positively-charged potassium ions exit the cell, beginning the process of repolarization. Their attempt to repolarize the atrial cells is short-lived however, because inward calcium current, conducted through voltage-gated L-type calcium channels (Ica(L)) keeps the cells in a state of depolarization just a bit longer, depicted as a plateau in the middle of the action potential waveform. The SA action potential does not need a calcium-based plateau current because SA cells are not responsible for contracting. Atrial cells, on the other hand, use the electrical depolarization from the action potential as the signal to contract. The “trigger” calcium entry through L-type channels during the plateau acts as a bridge between the electrical depolarization and mechanical contraction. The L-type channels inactivate rapidly, calcium current ceases, and then potassium exit, through multiple channels including the “ultra-rapid”-opening IKur, the “rapid” opening IKr (also called hERG channels) and the “slowly” opening IKs channels, fully repolarizes the cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

F1-ad-7-5-635: Atrial Action Potential Ion Currents. While the SA cells are depolarizing, the surrounding contractile cells of the atria are at their resting membrane potential of approximately -90mV, due to the IK1 current. Once the SA depolarizes, it promptly passes depolarizing positive ions to the atrial cells through low resistance gap junction channels. These positive ions bring the atrial cells to their own threshold potential, opening voltage-gated sodium channels (INa) in the atrial cell membranes, so that the atrial cells fire their own action potentials. At the peak of the upstroke in the atria, transient outward (Ito) potassium channels open; positively-charged potassium ions exit the cell, beginning the process of repolarization. Their attempt to repolarize the atrial cells is short-lived however, because inward calcium current, conducted through voltage-gated L-type calcium channels (Ica(L)) keeps the cells in a state of depolarization just a bit longer, depicted as a plateau in the middle of the action potential waveform. The SA action potential does not need a calcium-based plateau current because SA cells are not responsible for contracting. Atrial cells, on the other hand, use the electrical depolarization from the action potential as the signal to contract. The “trigger” calcium entry through L-type channels during the plateau acts as a bridge between the electrical depolarization and mechanical contraction. The L-type channels inactivate rapidly, calcium current ceases, and then potassium exit, through multiple channels including the “ultra-rapid”-opening IKur, the “rapid” opening IKr (also called hERG channels) and the “slowly” opening IKs channels, fully repolarizes the cells.
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