Ionic mechanism of delayed afterdepolarizations in ventricular cells isolated from human end-stage failing hearts

Article

关键词: TRANSIENT INWARD CURRENT;    SODIUM-CALCIUM EXCHANGE;    ACTIVATED CHLORIDE CURRENT;    FERRET PAPILLARY-MUSCLE;    CARDIAC PURKINJE-FIBERS;    GUINEA-PIG;    ACTION-POTENTIALS;    POTASSIUM CURRENT;    CA2+ RELEASE;    CL CURRENT;   

DOI  :  10.1161/hc4701.099577

来源: SCIE

【 摘 要 】

Background-Animal studies have shown that the Ca2+-activated Cl- current (I-Cl/Ca) and the Na-/Ca2- exchange current (I-Na/Ca) contribute to the transient inward current (I-ti). I-tt is responsible for the proarrhythmic delayed afterdepolarizations (DADs). We investigated the ionic mechanism of I-ti and DADs in human cardiac cells. Methods and Results-Human ventricular cells were enzymatically isolated from explanted hearts of patients with end-stage heart failure and studied with patch-clamp methodology. I(u)s were elicited in the presence of 1 mu mol/L norepinephrine by trains of repetitive depolarizations from -80 to +50 mV. DADs were induced in the presence of I mu mol/L norepinephrine at a stimulus frequency of 1 Hz. I-ti currents were inwardly directed over the voltage range between -110 and + 50 mV. Neither the Cl- channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid nor changes in [CF-](i) affected I-ti or DAD amplitude. This excludes an important role for I-ClCa. Blockade of Na+/Ca2+ exchange by substitution of all extracellular Na+ by Li+, conversely, completely inhibited I-ti, In rabbit, I-ClCa density in ventricular cells isolated from control hearts did not differ significantly from that in ventricular cells isolated from failing hearts. Conclusions-In contrast to many animal species, I-ti and DADs in human ventricular cells from failing lie Arts consist only of I-Na/Ca rabbits, heart failure per se does not alter I-ClCa, density, suggesting that I-ClCa may also be absent during DADs in nonfailing human ventricular cells.

【 授权许可】

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