Spontaneous neuronal activity in organotypic cultures of mouse dorsal rootganglion leads to upregulation ion of calcium channel expression on remoteSchwann cells

It is well established that neurons regulate the properties of both central and peripheral glial cells. Some of these neuro-glial interactions are mod ulated by the pattern of neuronal electrical activity. In the present work, we asked whether blocking the electrical activity of dorsal root ganglion (DRG) neurons in vitro by a chronic treatment with tetrodotoxin (TTX) would modulate the expression of the T-type Ca2+ channel by mouse Schwann cells. When recorded in their culture medium, about one-half of the DRG neurons s pontaneously fired action potentials (APs). Treatment for 4 days with 1 mu M TTX abolished both spontaneous and evoked APs in DRG neurons and in paral lel significantly reduced the percentage of Schwann cells expressing Ca2+ c hannel currents. On the fraction of Schwann cells still expressing Ca2+ cha nnel currents, these currents had electrophysiological parameters (mean amp litude, mean inactivation time constant, steady-state inactivation curve) s imilar to those of control cultures. Cotreatment for 4 days with 1 mu M TTX and 2 mM CPT-cAMP, a cAMP analogue that induces the expression de novo of Ca2+ channel currents in Schwann cells deprived of neurons, maintained the percentage of Schwann cells expressing Ca2+ channel currents, showing that TTX does not directly affect the expression of Ca2+ channel currents by Sch wann cell. We conclude that blocking spontaneous activity of DRG neurons in vitro downregulates Ca2+ channel expression by Schwann cells. These result s strongly suggest that DRG neurons upregulate Ca2+ channel expression by S chwann cells via the release of a diffusible factor whose secretion is depe ndent on electrical activity. (C) 2000 Wiley-Liss, Inc.