Prolonged exposure to
manganese in mammals may cause an
extrapyramidal disorder characterized by
dystonia and rigidity.
Gliosis in the pallidal segments underlies the well-established phase of the intoxication. The early phase of the intoxication may be characterized by psychic, nonmotor signs, and its morphological and electrophysiological correlates are less defined. In a rat model of
manganese intoxication (20 mg/ml in
drinking water for 3 months), neither neuronal loss nor
gliosis was detected in globus pallidus (GP). However, a striking vulnerability of
manganese-treated GP neurons emerged. The majority of GP neurons isolated from
manganese-treated rats died following brief incubation in standard dissociation media. In addition, patch-clamp recordings in the whole-cell configuration were not tolerated by surviving GP neurons. Neither coeval but untreated GP neurons nor striatal ones manifested analogous susceptibility. Using the perforated-patch mode of recording we attempted at identifying the functional hallmarks of GP vulnerability: in particular, voltage-gated
calcium currents and
glutamate-induced currents were examined.
Manganese-treated GP neurons exhibited
calcium currents similar to control cells aside from a slight reduction in the
dihydropyridine-sensitive current facilitation. Strikingly,
manganese-treated GP cells--but not striatal ones--manifested peculiar responses to
glutamate, since repeated applications of the
excitatory amino acid, at concentrations which commonly promote desensitizing responses, produced instead an irreversible cell damage. Possible mechanisms are discussed.