title: The selective A-type K+ current blocker Tx3-1 isolated from the Phoneutria nigriventer venom enhances memory of naïve and Aβ(25-35)-treated mice.
abstract: Potassium channels regulate many neuronal functions, including neuronal excitability and synaptic plasticity, contributing, by these means, to mnemonic processes. In particular, A-type K(+) currents (IA) play a key role in hippocampal synaptic plasticity. Therefore, we evaluated the effect of the peptidic toxin Tx3-1, a selective blocker of IA currents, extracted from the venom of the spider Phoneutria nigriventer, on memory of mice. Administration of Tx3-1 (i.c.v., 300 pmol/site) enhanced both short- and long-term memory consolidation of mice tested in the novel object recognition task. In comparison, 4-aminopyridine (4-AP; i.c.v., 30-300 pmol/site), a non-selective K(+) channel blocker did not alter long-term memory and caused toxic side effects such as circling, freezing and tonic-clonic seizures. Moreover, Tx3-1 (i.c.v., 10-100 pmol/site) restored memory of Aβ25-35-injected mice, and exhibited a higher potency to improve memory of Aβ25-35-injected mice when compared to control group. These results show the effect of the selective blocker of IA currents Tx3-1 in both short- and long-term memory retention and in memory impairment caused by Aβ25-35, reinforcing the role of IA in physiological and pathological memory processes.
authors.affiliation: Graduation Program in Biological Sciences, Toxicological Biochemistry, Building 18, Room 2203, Center of Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Guilherme M
authors.initials: GM
authors.lastname: Gomes
authors.forename: Gerusa D
authors.initials: GD
authors.lastname: Dalmolin
authors.forename: Marta do Nascimento
authors.initials: Mdo N
authors.lastname: Cordeiro
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Gomez
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Maribel A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D015761:4-Aminopyridine / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009479:Neuropeptides / Q000302:isolation & purification / Q000494:pharmacology*; D009498:Neurotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D015221:Potassium Channels; D021641:Recognition, Psychology; D013111:Spider Venoms / Q000737:chemistry*; D013112:Spiders / Q000737:chemistry
chemical_list: D009479:Neuropeptides; D009498:Neurotoxins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013111:Spider Venoms; C098736:Tx3 neurotoxin; D015761:4-Aminopyridine
keywords: A-type K(+) currents; Alzheimer's disease; Memory; Novel object recognition task