The role of the sodium-calcium exchanger for calcium extrusion in coronaryarteries

Calcium ionophores, such as the A23187, cause endothelium-dependent relaxat ion of arterial strips with intact endothelium, whereas the effect of the i onophore should result from the combination of a relaxation caused by the e ndothelium-dependent factors and of a contraction of the smooth muscles, In addition, the application of a calcium ionophore to a strip of pig coronar y arteries without endothelium does not change cytosolic free calcium conce ntration and force developed by the smooth muscle cells. To explain these p aradoxes, the hypothesis that active calcium extrusion would match the entr y of extracellular calcium caused by the ionophore was tested. We see that the sodium-calcium exchanger extrudes calcium that enters the smooth muscle cells in the absence of the ionophore. This exchanger is efficient enough to expel the increased influx of calcium created by the additional calcium carriers formed by the ionophore. This explains the inefficiency of calcium ionopholes to increase cytosolic free calcium of smooth muscle cells and c onsequently, the fact that the ionophore does not cause a contraction of a strip without endothelium. This makes evident that a calcium ionophore full y relaxes, in an endothelium-dependent manner, an intact strip of porcine c oronary artery. (C) 2000 Elsevier Science Inc. All rights reserved.