Extracellular calcium-sensing receptor induces cellular proliferation and activation of a nonselective cation channel in U373 human astrocytoma cells.

A receptor for extracellular calcium ions (Ca2+o), cloned from parathyroid gland, serves a critical function in Ca2+o homeostasis by regulating PTH release via "sensing" of its physiological agonist, Ca2+o. Its cloning from rat striatum revealed that the extracellular calcium-sensing receptor (CaR) could be involved in sensing ambient Ca2+o within the brain, where Ca2+ plays key roles in virtually all aspects of central nervous system (CNS) function. The CaR is expressed in neurons, oligodendrocytes, microglia and the human astrocytoma cell line, U87 where its functions include control of cellular proliferation and modulation of ion channels, such as outward K+ channels and nonselective cation channels (NCC). In this report, we have shown that the CaR is expressed in U373 cells as assessed by RT-PCR using CaR-specific primers followed by sequencing of the amplified products, by Northern blot analysis using a CaR-specific probe as well as by Western analysis utilizing a specific polyclonal anti-CaR antiserum. Furthermore, agents known to activate the cloned CaR induce increases in cellular proliferation and the open probability of an NCC. Thus our study strongly suggests that elevated levels of Ca2+o, acting via the CaR, activate an NCC that could contribute to the associated CaR-induced stimulation of proliferation.