Spontaneous neuronal activity in organotypic cultures of mouse dorsal root ganglion leads to upregulation of calcium channel expression on remote Schwann cells

Abstract

It is well established that neurons regulate the properties of both central and peripheral glial cells. Some of these neuro-glial interactions are modulated 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 spontaneously fired action potentials (APs). Treatment for 4 days with 1 μM TTX abolished both spontaneous and evoked APs in DRG neurons and in parallel significantly reduced the percentage of Schwann cells expressing Ca2+ channel currents. On the fraction of Schwann cells still expressing Ca2+ channel currents, these currents had electrophysiological parameters (mean amplitude, mean inactivation time constant, steady-state inactivation curve) similar to those of control cultures. Co-treatment for 4 days with 1 μM 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 Schwann cell. We conclude that blocking spontaneous activity of DRG neurons in vitro downregulates Ca2+ channel expression by Schwann cells. These results strongly suggest that DRG neurons upregulate Ca2+ channel expression by Schwann cells via the release of a diffusible factor whose secretion is dependent on electrical activity. GLIA 29:281–287, 2000. © 2000 Wiley-Liss, Inc.