Serum deprivation and NGF induce and modulate voltage-gated Na+ currents in human astrocytoma cell lines

✍ Scribed by Robert Kraft; Daniel Basrai; Klaus Benndorf; Stephan Patt

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 245 KB
• Volume: 34
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.1040

✦ Synopsis

Abstract

Glial tumor cells derived from primary tissue express large voltage‐gated Na^+^ currents, whereas glioma cell lines usually lack this feature. We studied the effect of serum deprivation on the expression of Na^+^ currents in two astrocytoma cell lines (1321N1 and A172). Serum deprivation for more than 2 days sufficed to induce large Na^+^ currents in both cell lines; 300 nM of the specific blocker of voltage‐gated Na^+^ channels, tetrodotoxin, blocked these currents by about 85%. During serum deprivation, the cells also underwent morphological changes that were characterized by cell rounding and outgrowth of processes. Treatment with 100 ng/ml nerve growth factor (NGF) promoted these morphological changes and also accelerated the development of Na^+^ currents. In 1321N1 cells, NGF increased the Na^+^ current density after short serum deprivation (3–6 d) and changed several gating properties after longer serum deprivation (9–13 d). In comparison with cells from the early culture stage (3–6 d), the steady‐state inactivation of the Na^+^ current was shifted by −24 mV in NGF‐treated cells from the late (9–13 d) culture stage. In untreated cells, this shift was only −13 mV. NGF accelerated the kinetics of inactivation and shifted the current‐voltage relationship in cells from the late culture stage by −14 mV. In A172 cells, most of these effects were present already after short serum deprivation either in presence or absence of NGF. It is concluded that in astrocytoma cells, Na^+^ currents are induced by serum deprivation and are modulated by NGF. This result supports the idea that NFG controls Na^+^ currents in these cells by autocrine stimulation. GLIA 34:59–67, 2001. © 2001 Wiley‐Liss, Inc.