Effects of extra- and intracellular calcium concentration on DNA replication,lateral growth,and differentiation of human epidermal cells in culture

Variation in the extra- and intra-cellular concentration of calcium ([Ca]e and [Ca]i) affected the 3H-thymidine labeling pattern of sorted S-phase cells in human epidermal cultures. A lowering of [Ca]e resulted in retarded lateral growth but, unless [Ca]e was extremely low, caused an increase in the proportion of strongly labelled (rapidly cycling) S-phase cells. An increased desquamation of superficial cells due to a reduced cellular cohesiveness was also observed in low calcium medium. Thus, a lowering of [Ca]e might stimulate the proliferation of a pool of cycling cells destined for rapid terminal differentiation and tissue regeneration, whereas proliferation destined for lateral growth is inhibited. Attempts to decrease the [Ca]i with the calcium chelator quin-2 at low [Ca]e seemed to elevate the proportion of strongly labelled S-phase cells, whereas an increased [Ca]i obtained with the ionophore A23187 caused a dramatic decrease in the proportion of S-phase cells that showed strong 3H-thymidine incorporation. This implies that variation in both [Ca]i and [Ca]e may play a role in the regulation of proliferation and differentiation, in keratinocytes.