The selective A-type K+ current blocker Tx3-1 isolated from the Phoneutria nigriventer venom enhances memory of naïve and Aβ25-35-treated mice

• Published in: Toxicon (Oxford) Vol. 76; pp. 23 - 27
• Main Authors: Gomes, Guilherme M., Dalmolin, Gerusa D., Cordeiro, Marta do Nascimento, Gomez, Marcus V., Ferreira, Juliano, Rubin, Maribel A.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 15.12.2013
• Subjects: 4-aminopyridine; A-type K+ currents; adverse effects; Alzheimer's disease; freezing; Memory; mice; Novel object recognition task; Phoneutria nigriventer; potassium; potassium channels; seizures; toxicity; venoms; Novel object recognition task; A-type K+ currents; Alzheimer's disease; Memory
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2013.08.059

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. •Tx3-1 enhances short-term and long-term memory of mice.•Tx3-1 rescue memory of Aβ25-35-treated mice.•Tx3-1 exhibited higher potency to improve memory in AD-like conditions.