Osteoblasts play a major role in bone formation. Osteoblasts employ intracellular Ca(2+) as a second messenger modulating hormonal responses and a cofactor for bone mineralization. Voltage-dependent Ca(2+) channels (VDCCs) are most commonly present in excitable cell membranes. They are also present at lower levels even in most nonexcitable cells too. In both types of cell, they mediate the influx of Ca(2+) in response to membrane depolarization. Prepulse facilitation is a phenomenon in which a long and strong depolarizing pulse induces a form of VDCC that exhibits an increased opening probability. We believe this to be the first study to demonstrate that strong depolarization prepulses both increase and decrease VDCCs in osteoblasts.