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Am J Physiol Cell Physiol 265: C1239-C1246, 1993;
0363-6143/93 $5.00
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AJP - Cell Physiology, Vol 265, Issue 5 C1239-C1246, Copyright © 1993 by American Physiological Society

ARTICLES

Ca2+ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts

Z. Wang, M. Estacion and L. J. Mordan
Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu 96813.

The role of low-threshold voltage-gated calcium channels (VGCC) in modulating extracellular calcium influx and proliferation was investigated in platelet-derived growth factor (PDGF)-stimulated C3H/10T1/2 mouse fibroblasts. Previous studies demonstrated that cell cycle progression after PDGF stimulation was dependent on extracellular calcium influx producing a sustained increase in the intracellular calcium concentration. In this study, PDGF-induced calcium influx, the sustained intracellular calcium increase, and progression to S phase were inhibited by nordihydroguariaretic acid (NDGA), an inhibitor of calcium influx through VGCC. With the use of the whole cell patch-clamp technique to measure calcium currents, NDGA inhibited inward calcium current through low-threshold VGCC, the only VGCC expressed in C3H/10T1/2 fibroblasts. The inhibitory effects of NDGA on calcium influx and cell proliferation each had a mean inhibitory dose of 2-3 microM. Although NDGA also effectively inhibits cyclooxygenase and lipoxygenase, the addition of prostaglandins or leukotrienes could not reverse this inhibition nor could it be replicated by other antioxidants. These data support the hypothesis that low-threshold VGCC can mediate extracellular calcium influx on the stimulation of cell proliferation by PDGF.


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