RUTHENIUM RED AS A TOOL TO STUDY CALCIUM CHANNELS, NEURONAL DEATH ANDTHE FUNCTION OF NEURAL PATHWAYS

The inorganic polycationic dye ruthenium red (RuR) exerts several effe cts on the nervous system when added in physiological solutions, both in vivo and in vitro. Part of these effects, including the paralysis o bserved in mammals after the systemic administration of RuR, can be ac counted for by the binding of RuR to nerve ending membranes, which res ults in inhibition of Ca2+ influx through voltage-sensitive calcium ch annels and the consequent inhibition of neurotransmitter release. On t he other hand, the administration of RuR into the cerebrospinal fluid induces intense convulsive activity, and its microinjection into the s ubstantia nigra reticulata or the hippocampus leads to various motor b ehavior alterations that can be related to hyperexcitability of the ne urons of the injected region. In addition, RuR penetrates the neuronal somata present in the area injected and induces cell destruction, whi ch has been interpreted as an excitotoxic action of the dye. The penet ration and the toxicity of RuR were also observed in primary neuronal cultures but did not occur in pure glial cultures, suggesting a select ive action on neurons. In the present article the in vitro and in vivo effects of RuR are reviewed and discussed in terms of the usefulness of the dye as an interesting tool to study calcium channels linked to transmitter release, neuronal death mechanisms and the function of neu ral pathways. Copyright (C) 1996 Elsevier Science Ltd