Regulation of Na+, K+ pump activity by nerve growth factor in chick embryo dorsal root ganglion cells

Abstract

Nerve growth factor (NGF) is required for the growth and development of sensory and sympathetic neurons. Incubation of chick dorsal root ganglionic cells without NGF resulted in a decrease of active (Na⁺, K⁺‐pump‐mediated) K⁺ influx over a period of several hours. Addition of NGF to NGF‐deprived cells caused (1) a return of the active K⁺ influx to the values occurring in cells continuously exposed to NGF, preceded by (2) a very rapid, but transient overstimulation of the Na⁺, K⁺‐pump‐mediated K⁺ influx. Restoration of normal Na⁺, K⁺‐pump activity occurred at NGF concentrations of 1 biological unit/ml or greater, whereas the NGF concentration in the 1–100 biological unit/ml range affected the rapidity with which the pump restoration took place. The transient pump behavior was only observed in NGF‐deprived cells and could not be elicited in NGF‐supported steady‐state cells or in cells having already received delayed NGF once. This transient Na⁺, K⁺‐pump behavior was exclusively displayed in conjunction with a high intracellular Na⁺ concentration. Decreasing the external Na⁺ concentration below 70 mM reduced the hyperstimulation response to NGF, until at 10 mM Na⁺ the delayed presentation of NGF caused no overshoot at all. The effect of NGF on the Na⁺, K⁺‐pump was specific for the NGF molecule and could not be mimicked by other proteins.