FUNCTIONAL LINKAGE OF NA-CA2+ EXCHANGE AND SARCOPLASMIC-RETICULUM CA2+ RELEASE MEDIATES CA2+ CYCLING IN VASCULAR SMOOTH-MUSCLE()

Ca2+ loss from the sarcoplasmic reticulum (SR) of rabbit inferior vena cava smooth muscle was monitored by measuring the decay of caffeine-i nduced fura-2 fluorescence transients. Removal of Ca2+ from the extrac ellular space caused a rapid loss of SR Ca2+ and a decline of cytoplas mic Ca2+ concentration ([Ca2+](i)). Simultaneous removal of extracellu lar Na+ greatly inhibited the rate of this (SR) Ca2+ loss. A rapid los s of SR Ca2+ was induced by 20 mu m CPA, regardless of the presence or absence of extracellular Na+ or Ca2+. These effects were not influenc ed by alterations in membrane potential owing to activity of Ca2+-acti vated K+ channels since 3 mM TEA had no effect on the rate of Ca2+ los s from the SR. These results indicate that when Ca2+ is removed from t he extracellular space, it induces Ca2+ release from the SR towards th e plasma membrane Na+-Ca2+ exchanger which subsequently translocates i t from the junctional cytoplasmic space to the extracellular space. Wh en the Na+-Ca2+ exchanger is arrested by removal of extracellular Naand Ca2+, Ca2+ released from the SR is re-sequestered by the sarco-end o-plasmic reticulum Ca2+-ATPase (SERCA). However, when both the Na+-Ca 2+ exchanger, and, the SERCA are blocked, Ca2+ released from the SR is extruded from the cells by the plasma membrane Ca2+-ATPase. These res ults reveal a hierarchy of interaction between the different Ca2+ tran sporters in the SR, and cell membranes.