The introduction of parathyroid hormone [bPTH (1-34)], 10(-8) M, into the medium of cultured rat osteoblasts results in rapid (less than 1 min) depolarization of the osteoblast membranes. Conventional and pH-sensitive microelectrodes were used to assess the mechanism underlying this change. PTH depolarized cell membrane independently of steady-state membrane potential (Vm). Blocking K+ conductance (Ba2+) and Ca2+-dependent K+ conductance (quinine) depolarized Vm by +13.1 +/- 4.6 (n = 6) and +14.8 +/- 6.7 mV (n = 6), respectively, and both abolished the effect of PTH on Vm. The rate of depolarization was reduced in low-Ca2+ medium. PTH inhibited low Na+-induced cell hyperpolarization, but intracellular pH was not altered by hormone addition. PTH-induced depolarization occurred even when the Na+-K+ pump was blocked with ouabain. A second slower response was seen in cells having a Vm lower than -60 mV, with an increase in negativity 5-15 min after hormone application. The results indicate that PTH rapidly modifies Vm by changes of K+ conductance, which may be the first step in hormonal stimulus-response coupling, and induces delayed, long-term changes in cell status.
