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

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.

Functional characterization of two isoforms of the P2Y-like receptor GPR17: [35S]GTPγS binding and electrophysiological studies in 1321N1 cells

“…Preliminary experiments performed in our laboratory demonstrated that Na ϩ and Ca 2ϩ channels are absent in 1321N1 astrocytoma cells, in agreement with literature data (24,34). The study was carried out on a total of 121 cells: 23 untransfected and 98 from hGPR17-expressing clones.…”

BK channel openers inhibit migration of human glioma cells

“…Previous data from our laboratory show that the human astrocytoma cell line 1321N1 expresses a variety of ion channels, including voltage-gated Na + and K + channels [11,12], inwardly rectifying K + channels [12], and largeconductance Ca 2+ -activated K + (BK) channels [2,12]. When a pipette solution containing a free [Ca 2+ ] of 10 nM was used, only large depolarizations induced whole-cell outward currents.…”

Peritumoral epilepsy: Relating form and function for surgical success

“…The subsequent acidosis leads to glial cell swelling and damage and it is possible that this may lead to increased seizure generation [32,72] . In lower grade tumors, localized acidity causes astrocytoma cells and malignant glial cells to demonstrate an increased Na + influx and may lead to increased cellular excitability [71,73] .…”