L‐type Ca2+ channel opener BayK 8644‐induced Ca2+ influx and Ca2+ release in human oral cancer cells (OC2)

AbstractThe effect of BayK 8644, a chemical widely used to activate L‐type Ca2+ channels, on cytosolic free Ca2+ concentrations ([Ca2+]i) in human oral cancer cells (OC2) has not been explored to date. The present study examined whether BayK 8644 altered basal [Ca2+]i levels in suspended OC2 cells by using fura‐2. BayK 8644 (10 pM–10 µM) increased [Ca2+]i in a concentration‐dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. BayK 8644‐induced Ca2+ influx was blocked by nifedipine, but was not altered by the store‐operated Ca2+ 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 A2 inhibitor, aristolochic acid. In Ca2+‐free medium, after pretreatment with 1 µM BayK 8644, 1 µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor)‐induced [Ca2+]i rises were abolished; and conversely, thapsigargin pretreatment abolished BayK 8644‐induced [Ca2+]i rises. Inhibition of phospholipase C with U73122 did not change BayK 8644‐induced [Ca2+]i rises. Collectively, in OC2 cells, BayK 8644 induced [Ca2+]i rises by causing phospholipase C‐independent Ca2+ release from the endoplasmic reticulum; and Ca2+ influx via L‐type Ca2+ channels. Drug Dev Res 69: 2008. © 2008 Wiley‐Liss, Inc.