Baartscheer A, Schumacher C A, Opthof T, Fiolet J W
Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands.
J Mol Cell Cardiol. 1996 Sep;28(9):1963-73. doi: 10.1006/jmcc.1996.0189.
Reversal of the driving force of the Na+/Ca(2+)-exchanger (delta Gexch) by a sufficiently large change of the transsarcolemmal electrochemical potential of sodium and calcium causes a transient increase of cytoplasmic calcium ([Ca2+]i). The objective of this study was to investigate the origin of this transient increase of calcium. In isolated quiescent rat ventricular myocytes delta Gexch was abruptly changed by reduction of extracellular sodium ([Na+]o), with or without a simultaneous increase of potassium ([K+]o) or calcium ([Ca2+]i). [Ca2+]i was measured with indo-1. A particular change of delta Gexch induced either by reduction of [Na+]o alone or in combination with increase of [Ca2+]o, produced a transient increase of [Ca2+]i of the same magnitude with a maximum after around 30s. The response of [Ca2+]i was insensitive to verapamil, but was greatly reduced by ryanodine, thapsigargin and caffeine, indicating a large contribution originating from the sarcoplasmic reticulum (SR). The magnitude of the response of [Ca2+]i and also the contribution from SR increased with increasing change of delta Gexch. A particular change of delta Gexch. Induced by a reduction of [Na+]o in combination with membrane depolarization (increase of [K+]o) increased the response of [Ca2+]i, compared that induced by reduction of [Na+]o alone at the same change of delta Gexch. This effect increased with the degree of depolarization, and was completely abolished by verapamil. Also in depolarized cells the response of [Ca2+]i was reduced by ryanodine. However, the contribution from SR to the response did not depend on the degree of depolarization, but only on the magnitude of the change of delta Gexch. Inhibition of the Na+/Ca(2+)-exchanger by Ni2+ almost completely abolished the response of [Ca2+]i to reduction of [Na+]o. Restitution of [Na+]o during the course of the calcium response greatly accelerated the rate of decay of [Ca2+]i. It is concluded that in quiescent rat ventricular myocytes, a large part of the transient increase of cytoplasmic calcium associated with reversal of the driving force of the Na+/Ca(2+)-exchanger originates from SR. Reversal of the exchanger combined with sustained depolarization increased the transient of [Ca2+]i, but the extra influx of calcium associated with depolarization did not affect the contribution from SR.
钠/钙交换体驱动力（ΔGexch）的逆转是由跨肌膜的钠和钙电化学势发生足够大的变化引起的，这会导致细胞质钙（[Ca2+]i）短暂增加。本研究的目的是探究这种钙短暂增加的来源。在分离的静止大鼠心室肌细胞中，通过降低细胞外钠（[Na+]o）突然改变ΔGexch，同时或不同时增加钾（[K+]o）或钙（[Ca2+]i）。用indo-1测量[Ca2+]i。单独降低[Na+]o或与增加[Ca2+]o联合诱导的ΔGexch的特定变化，产生相同幅度的[Ca2+]i短暂增加，在约30秒后达到最大值。[Ca2+]i的反应对维拉帕米不敏感，但被Ryanodine、毒胡萝卜素和咖啡因大大降低，表明很大一部分源自肌浆网（SR）。[Ca2+]i反应的幅度以及SR的贡献随着ΔGexch变化的增加而增加。由降低[Na+]o并结合膜去极化（增加[K+]o）诱导的ΔGexch的特定变化，与在相同ΔGexch变化下单独降低[Na+]o诱导的相比，增加了[Ca2+]i的反应。这种效应随着去极化程度的增加而增加，并被维拉帕米完全消除。同样在去极化细胞中，[Ca2+]i的反应也被Ryanodine降低。然而，SR对反应的贡献不取决于去极化程度，而仅取决于ΔGexch变化的幅度。Ni2+对钠/钙交换体的抑制几乎完全消除了[Ca2+]i对降低[Na+]o的反应。在钙反应过程中恢复[Na+]o大大加速了[Ca2+]i的衰减速率。得出的结论是，在静止大鼠心室肌细胞中，与钠/钙交换体驱动力逆转相关的细胞质钙短暂增加的很大一部分源自SR。交换体的逆转与持续去极化相结合增加了[Ca2+]i的瞬变，但与去极化相关的额外钙内流不影响SR的贡献。
