Antiepileptic effects of cobalt, manganese and magnesium on bicuculline-induced epileptiform activity in hippocampal neurons

Abstract

Background: Calcium signaling is described as a relevant factor in synchronization of neurons and increased excitability in epileptogenesis. Aim of the present investigations was to test the antiepileptic effect of the classical inorganic calcium channel blockers cobalt (Co²⁺), manganese (Mn²⁺) and magnesium (Mg²⁺).

Methods: Experiments were carried out on hippocampal slices of guinea pigs. Epileptiform field potentials (EFP) were elicited by adding bicuculline (10 µmol/l) to the artificial cerebrospinal fluid (CSF). Kalium was elevated from normal (4 mmol/l) to 8 mmol/l. Co²⁺ (CoCl₂; 2, 1, 0.5 and 0.1 mmol/l), Mn²⁺ (MnCl₂; 2, 1, 0.5 and 0.1 mmol/l) and Mg²⁺ (MgCl₂; 8, 6, 5, 4 and 2 mmol/l) were added to the superfusate.

Results: Concentrations of 2, 1 and 0.5 mmol/l Co²⁺, 2 and 1 mmol/l Mn²⁺ and 8 respectively 6 mmol/l Mg²⁺ were able to suppress EFP sufficient in a dose dependent manner. In concentrations of 0.1 mmol/l Co²⁺, 0.5 mmol/l and 0.1 mmol/l Mn²⁺ and 5 respectively 4 and 2 mmol/l Mg²⁺ suppression was incomplete. With washout of the inorganic calcium channel blockers the EFP reappeared.

Discussion: All tree inorganic calcium channel blockers were able to suppress EFP in a dosage dependent and reversible manner. Weak reappearance of EFP after washout of Co²⁺ might be due to additional cytotoxic effects. The following mechanisms may contribute: i) blockade of voltage-activated calcium channels in the postsynaptic membrane, ii) changes in the activation of voltage-dependent sodium channels, iii) blockade of synaptic transmission.

Keywords: Calcium channel blocker; Cobalt; Epilepsy; Magnesium; Manganese.