Cellular Basis of Abnormal Calcium Transients of Failing Human Ventricular Myocytes

ABSTRACT—Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca]i. This study examined the respective roles of the L-type Ca current (ICa), SR Ca uptake, storage and release, Ca transport via the Na-Ca exchanger (NCX), and Ca buffering in the a...

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Veröffentlicht in:Circulation research 2003-04, Vol.92 (6), p.651-658
Hauptverfasser: Piacentino, Valentino, Weber, Christopher R, Chen, Xiongwen, Weisser-Thomas, Jutta, Margulies, Kenneth B, Bers, Donald M, Houser, Steven R
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Sprache:eng
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Zusammenfassung:ABSTRACT—Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca]i. This study examined the respective roles of the L-type Ca current (ICa), SR Ca uptake, storage and release, Ca transport via the Na-Ca exchanger (NCX), and Ca buffering in the altered Ca transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca uptake rates by the SR and the amount of Ca stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca]i, ICa density, or cellular Ca buffering. However, Ca influx during the late portions of the action potential seems able to elevate [Ca]i in F but not in NF myocytes. A reduction in the rate of net Ca uptake by the SR slows the decay of the Ca transient and reduces SR Ca stores. This leads to reduced SR Ca release, which induces additional Ca influx during the plateau phase of the action potential, further slowing the decay of the Ca transient. These changes can explain the defective Ca transients of the failing human ventricular myocyte.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000062469.83985.9B