Changes in excitability of CA1 pyramidal neurons in slices prepared from AlCl3-treated rabbits.
Intracellular recordings in 'in vitro' hippocampal slices, prepared from intracisternally AlCl3-intoxicated rabbits, were obtained from 43 CA1 pyramidal neurons. The experiments were performed 12-20 days after aluminum administration. The electrotonic length was significantly shorter than that of 33 control neurons, in agreement with morphological evidence of an Al-induced dendritic impairment. Both postsynaptic and Ca2(+)-dependent K+ hyperpolarizing potentials were also found to be significantly decreased, with reciprocal enhancement of excitatory postsynaptic potentials and depolarizing after-potentials. The former finding is ascribed to a selective neurotoxic effect of aluminum on GABAergic interneurons; the latter can be accounted for by an Al-induced increase in cyclic AMP, which is known to block the Ca2(+)-activated K+ conductance responsible for after-hyperpolarizing potentials. It is concluded that aluminum can exert its epileptogenic effect through multiple neurotoxic mechanisms involving membrane electrotonic properties, K+ conductances, and synaptic influences, thus resulting in a neuronal hyperexcitable state. Such changes are detectable in the early stages of the Al-induced encephalopathy, when there is only slight evidence of cytoskeleton alterations (i.e., neurofibrillary degeneration).
Franceschetti
S
S
Dept. of Neurophysiology, Istituto Neurologico C. Besta, Milan, Italy.
Bugiani
O
O
Panzica
F
F
Tagliavini
F
F
Avanzini
G
G
D000200:Action Potentials / Q000187:drug effects; D000535:Aluminum / Q000633:toxicity*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology; D001933:Brain Stem / Q000473:pathology*; D002712:Chlorides / Q000633:toxicity*; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009410:Nerve Degeneration; D011817:Rabbits
D017607:Aluminum Compounds; D002712:Chlorides; D000077410:Aluminum Chloride; D000535:Aluminum