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-induced fura-2 fluorescence transients. Removal of Ca2+ from the extracellular space caused a rapid loss of SR Ca2+ and a decline of cytoplasmic Ca2+ concentration ([Ca2+](i)). Simultaneous removal of extracellular Na+ greatly inhibited the rate of this (SR) Ca2+ loss. A rapid loss 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 influenced by alterations in membrane potential owing to activity of Ca2+-activated K+ channels since 3 mM TEA had no effect on the rate of Ca2+ loss from the SR. These results indicate that when Ca2+ is removed from the extracellular space, it induces Ca2+ release from the SR towards the plasma membrane Na+-Ca2+ exchanger which subsequently translocates it from the junctional cytoplasmic space to the extracellular space. When the Na+-Ca2+ exchanger is arrested by removal of extracellular Na+ and Ca2+, Ca2+ released from the SR is re-sequestered by the sarco-endo-plasmic reticulum Ca2+-ATPase (SERCA). However, when both the Na+-Ca2+ exchanger, and, the SERCA are blocked, Ca2+ released from the SR is extruded from the cells by the plasma membrane Ca2+-ATPase. These results reveal a hierarchy of interaction between the different Ca2+ transporters in the SR, and cell membranes.