Restorative effects of cyclic AMP on complex bioelectric activities of cultured fetal rodent CNS tissues after acute CA⁺⁺‐deprivation

Explants of fetal mouse spinal cord and cerebral cortex generate organotypic slow‐wave and repetitive‐spike discharges in vitro which can be abolished by agents which reduce the concentration of Ca ++ available to the tissue. Synaptically mediated discharges are rapidly blocked in Ca ++ ‐free balanced salt solution (BSS), or in regular BSS after addition of 10 −3 M EGTA, 5–10 × 10 −3 M Mg ++ , or 10 −4 M xylocaine, but simple spike potentials can still propagate. When low concentrations of cyclic AMP or dibutyryl cyclic AMP (2 × 10 −6 M) are added to the Ca ++ ‐free BSS or Ca ++ ‐antagonist‐BSS, a temporary (1–20 min) restoration of characteristic complex bioelectric activities occurs (or the onset of depression is delayed if cyclic AMP is initially added). Phosphodiesterase inhibitors, e.g. 10 −3 M caffeine, are also effective in restoring these blockades, whereas 5′AMP and ATP are not. Application of 10 −6 M cyclic AMP or 10 −3 M caffeine in regular BSS greatly enhances excitability of some CNS explants, resembling convulsive effects observed in CNS in situ . The data suggest that cyclic AMP can mobilize Ca ++ from membranebound Ca pools within neurons in CNS explants so as to permit Ca ++ ‐dependent release of neurotransmitter during Ca ++ deficits. Thus, it may also be that under normal conditions, cyclic AMP can regulate the availability of Ca ++ for synaptic transmission in the central nervous system, thereby modulating the efficacy of synaptic functions.