ROLE OF EPIDERMAL GROWTH FACTOR-INDUCED MEMBRANE DEPOLARIZATION AND RESULTING CALCIUM INFLUX IN OSTEOBLASTIC CELL-PROLIFERATION

This study investigated the effects of epidermal growth factor (EGF) o n the membrane potential of rat calvarial osteoblasts, in order to und erstand the mechanism responsible for calcium influx and the role thes e EGF-induced events have in osteoblastic cell proliferation. Changes in plasma membrane potential were measured using patch clamp technique s in isolated cells, EGF induced changes in plasma membrane potential only after cells had been in culture for at least 6 days. EGF induced membrane depolarization in 55% of rat calvarial osteoblasts studied af ter 6 to 8 days in culture. This membrane event was dependent on extra cellular calcium, therefore, one or more calcium conductances were inv olved, Nifedipine, a voltage-activated calcium channel blocker, signif icantly reduced membrane depolarization, and demonstrated the existenc e of a nifedipine-insensitive conductance. Osteoblastic cell prolifera tion was measured by cell count. The EGF-dependent increase in cell pr oliferation was blocked by addition of 10 mu M nifedipine. Therefore, it appears that the mechanism of action of EGF-induced osteoblastic ce ll proliferation is mediated by changes in plasma membrane potential w hich result in extracellular calcium influx.