title: Augmentation and ionic mechanism of effect of beta-N-methylamino-L-alanine in presence of bicarbonate on membrane potential of Retzius nerve cells of the leech Haemopis sanguisuga.
abstract: The role of neurotoxic non-protein amino acid beta-N-methylamino-L-alanine (L-BMAA) as a putative causative agent of Western pacific amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC) has recently been reinvigorated. In view of this data we have investigated the strength and mechanism of effect of L-BMAA in presence of 20 mmol/L bicarbonate (a cofactor for BMAA) on membrane potential of the Leech Haemopis sanguisuga. Our results show that L-BMAA has excitatory effect in bicarbonate containing solution, which is more potent than in nominally bicarbonate free solution. This potentiation by bicarbonate is L-BMAA specific, as it was not exhibited by beta-N-oxalylamino-L-alanine. The effect of L-BMAA was partially blocked by non-NMDA receptor antagonist CNQX. Application of L-BMAA caused a decrease in input membrane resistance, an increase of intracellular sodium activity, and a decrease of intracellular potassium activity. Present findings indicate that BMAA could initiate excitotoxicity through activation of non-NMDA ionotropic glutamate receptors.
authors.affiliation: Institute for Pathological Physiology, Medical faculty Belgrade, Belgrade, Serbia. slopicic@med.bg.ac.yu
authors.forename: Srdjan
authors.initials: S
authors.lastname: Lopicic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nedeljkov
authors.forename: Dusan
authors.initials: D
authors.lastname: Cemerikic
mesh_terms: D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D000087522:Cyanobacteria Toxins; D007865:Leeches / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology
chemical_list: D000599:Amino Acids, Diamino; D001639:Bicarbonates; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; D017470:Receptors, Glutamate; C001824:beta-N-methylamino-L-alanine