A role for the sarcoplasmic reticulum in Ca2+ extrusion from rabbit inferior vena cava smooth muscle

Ca2+ extrusion from rabbit inferior vena cava smooth muscle was studied using ratiometric fura 2 fluorimetry. Concomitant blockade of the plasma membrane Ca2+-adenosinetriphosphatase (ATPase; PCMA), Na+-Ca2+ exchanger, and sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) completely prevented the decline in intracellular Ca2+ concentration ([Ca2+](i)) normally observed when Ca2+ is removed from the extracellular space (ECS) after stimulated Ca2+ influx. Blockade of the Na+-Ca2+ exchanger by removal of external Na+ reduced the rate of [Ca2(+)](i) decline by 47%. Blockade of SERCA with cyclopiazonic acid reduced it by 23%, and this was not additive to the effects of Na+ removal. Exposure to nominally Ca2+-free solution prevented the sarcoplasmic reticulum (SR) from reloading only if the Na+-Ca2+ exchanger was operational. Our results can be explained by an SR contribution to Ca2+ extrusion in which SERCA is arranged in series with Na+-Ca2+ exchange.