The action of MPTP on synaptic transmission is affected by changes in Ca2+ concentrations.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a disruption of nigrostriatal dopaminergic function which resembles parkinsonism. On the cellular level, the disruption involves a Ca2+ independent release of dopamine, depletion of nigral and striatal dopamine, and the death of dopaminergic neurons. We have previously reported that MPTP can cause a non-reversible inhibition of neostriatal synaptic transmission. In this study we investigated the effect of altering Ca2+ concentration on MPTP's actions in the mouse nigrostriatal brain slice. We report finding that the MPTP induced non-reversible decrease in N-2 amplitude did not occur if synaptic transmission had been blocked using a low Ca2(+)-high Mg2+ artificial cerebrospinal fluid (ACSF) during MPTP application. Low Ca2(+)-high Mg2+ ACSF did not however alter the decrease in slice dopamine content caused by MPTP. These data provide initial support for the hypothesis that MPTP's ability to alter functional synaptic transmission is Ca2+ dependent whereas its releasing action on dopamine is Ca2+ independent.