Chapter Four Sodium–Calcium Exchanger in Pig Coronary Artery

This review focuses on the sodium-calcium exchangers (NCX) in the left anterior descending coronary artery smooth muscle. Bathing tissues in Na⁺-substituted solutions caused them to contract. In cultured smooth muscle cells, it increased the cytosolic Ca²⁺ concentration and extracellular entry of ⁴⁵Ca²⁺. All three activities were attributed to NCX since they were inhibited by NCX inhibitors. The tissues also expressed the sarco/endoplasmic reticulum (SER) Ca²⁺ pump SERCA2b whose activity was much greater than that of NCX. Inhibiting SERCA2b with thapsigargin decreased the NCX-mediated ⁴⁵Ca²⁺ accumulation by the cells. The decrease was not observed in cells loaded with the Ca²⁺-chelator BAPTA. The results are consistent with a limited diffusional space model with a proximity between NCX and SERCA2b. NCX molecules appear to be colocalized with the subsarcolemmal SERCA2b based on studies on membrane flotation experiments and microscopic fluorescence imaging of antibody-labeled cells. Thapsigargin inhibition of SERCA2b moved NCX even closer to SER. This provides a model for the NCX-mediated Ca²⁺ refilling of SER in the arterial smooth muscle. The model for the NCX-mediated refilling of the depleted SER proposed for smooth muscle did not apply to endothelium in which NCX levels were greater and SERCA levels were lower than in smooth muscle. The effect of thapsigargin on the NCX-mediated Ca²⁺ accumulation which was observed in smooth muscle was absent in the endothelium. We propose that the coupling between NCX and smooth muscle may be tissue dependent.