The Benefits of Reducing the Cardiac Late Sodium Current

来源 :BITs 1rd Annual World Cancer Congress of Cardiology-2009(200 | 被引量 : 0次 | 上传用户:Shauphei
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  Cardiac voltage-gated Na+ channels (NaV1.5) open very briefly every cardiac cycle (leading to cell depolarization and the upstroke of the action potential) then enter an inactivated state for the duration of the action potential (AP) plateau.A small fraction ofNa+ channels do not inactivate completely, however, and their late openings create late Na+ current (late INa) throughout the cardiac systolic period.Late INa is normally small but is increased in pathological states such as ischemia and heart failure.The enhancement of late INa in these states contributes to action potential prolongation, arrhythmic activity (EADs and DADs), and ventricular stiffening (slowing of relaxation).Late INa leads to an increase of the intracellular concentration of Na+, and Na+ loading may lead to Ca2+ overload via Na+/Ca2+ exchange.Because CaMKⅡ activation by Ca2+ can itself lead to phosphorylation of the Na+ channel and a further increase of late INa, there is a positive feedback loop between increases of late INa and cellular calcium accumulation.
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