L‐type Ca 2+ channel opener BayK 8644‐induced Ca 2+ influx and Ca 2+ release in human oral cancer cells (OC2)

The effect of BayK 8644, a chemical widely used to activate L‐type Ca 2+ channels, on cytosolic free Ca 2+ concentrations ([Ca 2+ ] i ) in human oral cancer cells (OC2) has not been explored to date. The present study examined whether BayK 8644 altered basal [Ca 2+ ] i levels in suspended OC2 cells by using fura‐2. BayK 8644 (10 pM–10 µM) increased [Ca 2+ ] i in a concentration‐dependent manner. The Ca 2+ signal was reduced partly by removing extracellular Ca 2+ . BayK 8644‐induced Ca 2+ influx was blocked by nifedipine, but was not altered by the store‐operated Ca 2+ entry inhibitors, econazole and SKF96365; protein kinase C modulators phorbol 12‐myristate 13‐acetate (PMA) and GF109203X; the protein kinase A inhibitor H89; and the phospholipase A 2 inhibitor, aristolochic acid. In Ca 2+ ‐free medium, after pretreatment with 1 µM BayK 8644, 1 µM thapsigargin (an endoplasmic reticulum Ca 2+ pump inhibitor)‐induced [Ca 2+ ] i rises were abolished; and conversely, thapsigargin pretreatment abolished BayK 8644‐induced [Ca 2+ ] i rises. Inhibition of phospholipase C with U73122 did not change BayK 8644‐induced [Ca 2+ ] i rises. Collectively, in OC2 cells, BayK 8644 induced [Ca 2+ ] i rises by causing phospholipase C‐independent Ca 2+ release from the endoplasmic reticulum; and Ca 2+ influx via L‐type Ca 2+ channels. Drug Dev Res 69: 2008. © 2008 Wiley‐Liss, Inc.