Serum triggers a sequence of rapid ionic conductance changes in quiescent neuroblastoma cells

Abstract

SERUM is required for the growth of nearly all animal cells in culture, but the mechanisms by which serum interacts with cells are largely unknown^1,2. Evidence exists, however, that the primary site of action of the serum constituents is at the plasma membrane. For example, the first detectable events following serum stimulation of resting fibroblasts involve alterations in membrane transport, such as a stimulation of the (Na⁺ + K⁺)ATPase^3,4 and an increase in the uptake of various nutrients⁵. Most of this evidence has been obtained using tracer flux techniques, but the relatively poor time resolution of this method (of the order of minutes) has precluded detection of dynamic membrane changes that may occur within seconds of serum addition. We have applied intracellular electrophysiological techniques in a search for rapid ionic membrane events following serum stimulation of mouse neuroblastoma cells. These cells stop growing (become ‘quiescent’) after serum removal and begin to extend neurites, but on re-addition of serum the neurites retract and cell division resumes^6,7. Here we report that the immediate consequence of adding fetal calf serum (PCS) to quiescent neuroblastoma cells is a triphasic membrane potential response, caused by a series of transient ionic permeability changes, the first of which is a rapid and transient increase in Na⁺ conductance. These conductance changes, which are distinctly different from those underlying electrical excitability, seem to be the first events following serum stimulation and may provide a clue to the mode of action of serum growth factors.