Regulation of Ca2+ Transport by Platelet-Derived Growth Factor-BB in Rat Vascular Smooth Muscle Cells

The present study investigates the effects of platelet-derived growth factor (PDGF) isoform BB (PDGF-BB) on cytosolic Ca concentration ([Ca]i), Ca transport, and Ca pools in rat vascular smooth muscle (VSM) cells. VSM cells from thoracic aorta of Milan normotensive rats were enzymatically dispersed, cultured in 10% serum medium, and made quiescent by 72 hours in 0.3% serum medium. [Ca]i, Ca influx, Ca efflux, and exchangeable cell Ca pool were evaluated by ratiometric fluorescent and radioisotope techniques. Ca transport showed time-dependent changes during stimulation with PDGF-BB. The initial early responses to this peptide were a transient rise in [Ca]i, a 30% decrease in Ca influx, and a 3.6-fold increase in the rate constant for active Ca efflux. Stimulation of Ca efflux and inhibition of Ca influx were associated with a substantial 30% reduction in the cell Ca pool. This initial stimulation of Ca efflux is concomitant with Ca mobilization into the cytosol and is due to activation of Na-independent Ca efflux via the Ca pump. After a 10 -minute stimulation, Ca influx returned to the basal value, whereas Ca efflux remained 2.2-fold above control values, leading to a decline in [Ca]i below basal levels and a further decrease in the cell Ca pool. Nearly half of this late Ca efflux appears to be driven by Na-Ca exchange, as evidenced by its external Na dependence. After a 120-minute stimulation with PDGF-BB, nifedipine-sensitive Ca influx is increased 37% above basal levels, and Ca efflux remains elevated. During prolonged stimulation by PDGF-BB, both Ca influx and efflux are stimulated, resulting in a new intracellular Ca homeostasis marked by the recovery of the cell Ca pool but a lowered [Ca]i. These final events coincide with the initiation of cell proliferation in VSM cells by PDGF-BB.