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.