Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression
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...• Drugs blocking the potassium ultra-rapid current (IKUR) gave disappointing results because of paradoxical shortening of APD and downregulation in AF patients.(221,222) TASK-1, a member of the two-pore-domain potassium current, is abundant in human atria but not in the ventricles, and is up-regulated in AF....
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...Other molecules interfere with intracellular calcium dynamics targeting Ca2þ-calmodulin dependent protein kinase activity(233) or ryanodine receptors.(221) • Some specific non-coding microRNAs are involved in atrial fibrosis and electrical remodelling in AF and represent attractive targets for new AAD therapies....
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Cites background from "Cellular and Molecular Electrophysi..."
...Computational modelling shows that increased total inward-rectifier Kþ current in chronic atrial fibrillation (cAF) is the major contributor to the stabilisation of re-entrant circuits by shortening APD and hyperpolarizing the resting membrane potential [41,116]....
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...Connexin-40 expression decreases in the PVs of dogs with AF-related remodelling, possibly due to tachycardia-induced connexin-degradation by calpains [41,116]....
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...Small-conductance Ca2þ-activated Kþ (SK) currents (ISK) also play a role in AF [41,116]....
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...Atrial tachycardia remodelling reduces Ca2þ-transient amplitude by a variety of mechanisms, contributing to atrial contractile dysfunction [41,116,124]....
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...2-translation and Ca2þ -dependent calpain activation, causing proteolytic breakdown of L-type Ca2þ channels [41,116]....
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504 citations
References
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"Cellular and Molecular Electrophysi..." refers background in this paper
...Role of the PVs PV sleeves play an important role in the initiation of AF.(48) The...
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"Cellular and Molecular Electrophysi..." refers background in this paper
...Largely as a major risk factor for embolic stroke and worsening heart failure (HF), AF is associated with significant morbidity and mortality.(3) AF is classified as paroxysmal AF (pAF) when episodes last <7 days and spontaneously convert to normal sinus rhythm, persistent AF when lasting ≥7 days, or permanent AF when no further attempts to achieve normal sinus rhythm are made....
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