{"title":"Selectively Blocking Small Conductance Ca<sup>2+</sup>-Activated K<sup>+</sup> Channels Improves Cognition in Aged Mice.","authors":"Jessie Ong, H Craig Heller, Elsa Pittaras","doi":"10.3390/biology14020149","DOIUrl":null,"url":null,"abstract":"<p><p>Aging is associated with decreased neuronal sensitivity and activity that creates deficits in cognitive processes, including learning, memory, motivation, general activity, and other behaviors. These effects are due in part to decreased intracellular Ca<sup>2+</sup> homeostasis, increasing hyperpolarization of the resting potential in aged neurons and therefore decreasing their excitability. To reduce hyperpolarization in aged mice, we used apamin, a selective small conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (sK<sub>Ca</sub>) channel blocker. By blocking the sK<sub>Ca</sub> channels, apamin decreases the egress of the K<sup>+</sup> out of the cell, reducing its hyperpolarization and causing it to be closer to threshold potential. As a result, neurons should be more sensitive to excitatory stimuli and more active. We evaluated the performance of aged mice in a selection of cognitive and behavioral tests prior to and after systemic applications of apamin or the vehicle saline. Apamin improved performance in short-term memory, increased attention to tasks, and decreased anhedonia. Apamin had no significant effect on long-term spatial and recognition memory, risk-taking behavior, sociability, and anxiety. Our results are compatible with the known effects of sK<sub>Ca</sub> channel blockade on neuronal sensitivity and activity; however, these short-term effects were not reflected in longer-term alterations of neural plasticity responsible for long-term spatial and recognition memory or other more complex cognitive processes we evaluated.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 2","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851921/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology-Basel","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/biology14020149","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
Selectively Blocking Small Conductance Ca2+-Activated K+ Channels Improves Cognition in Aged Mice.
Aging is associated with decreased neuronal sensitivity and activity that creates deficits in cognitive processes, including learning, memory, motivation, general activity, and other behaviors. These effects are due in part to decreased intracellular Ca2+ homeostasis, increasing hyperpolarization of the resting potential in aged neurons and therefore decreasing their excitability. To reduce hyperpolarization in aged mice, we used apamin, a selective small conductance Ca2+-activated K+ (sKCa) channel blocker. By blocking the sKCa channels, apamin decreases the egress of the K+ out of the cell, reducing its hyperpolarization and causing it to be closer to threshold potential. As a result, neurons should be more sensitive to excitatory stimuli and more active. We evaluated the performance of aged mice in a selection of cognitive and behavioral tests prior to and after systemic applications of apamin or the vehicle saline. Apamin improved performance in short-term memory, increased attention to tasks, and decreased anhedonia. Apamin had no significant effect on long-term spatial and recognition memory, risk-taking behavior, sociability, and anxiety. Our results are compatible with the known effects of sKCa channel blockade on neuronal sensitivity and activity; however, these short-term effects were not reflected in longer-term alterations of neural plasticity responsible for long-term spatial and recognition memory or other more complex cognitive processes we evaluated.
期刊介绍:
Biology (ISSN 2079-7737) is an international, peer-reviewed, quick-refereeing open access journal of Biological Science published by MDPI online. It publishes reviews, research papers and communications in all areas of biology and at the interface of related disciplines. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.