BK channels sustain neuronal Ca 2+ oscillations to support hippocampal long-term potentiation and memory formation.
Thomas PhamTamara HusseinDila CalisHelmut BischofDavid SkrabakMelanie Cruz SantosSelina MaierDavid SpähnDaniel KalinaStefanie SimonsigRebekka EhingerBernhard GroschupMarlies KnipperNikolaus PlesnilaPeter RuthRobert LukowskiLucas MattPublished in: Cellular and molecular life sciences : CMLS (2023)
Mutations of large conductance Ca 2+ - and voltage-activated K + channels (BK) are associated with cognitive impairment. Here we report that CA1 pyramidal neuron-specific conditional BK knock-out (cKO) mice display normal locomotor and anxiety behavior. They do, however, exhibit impaired memory acquisition and retrieval in the Morris Water Maze (MWM) when compared to littermate controls (CTRL). In line with cognitive impairment in vivo, electrical and chemical long-term potentiation (LTP) in cKO brain slices were impaired in vitro. We further used a genetically encoded fluorescent K + biosensor and a Ca 2+ -sensitive probe to observe cultured hippocampal neurons during chemical LTP (cLTP) induction. cLTP massively reduced intracellular K + concentration ([K + ] i ) while elevating L-Type Ca 2+ channel- and NMDA receptor-dependent Ca 2+ oscillation frequencies. Both, [K + ] i decrease and Ca 2+ oscillation frequency increase were absent after pharmacological BK inhibition or in cells lacking BK. Our data suggest that L-Type- and NMDAR-dependent BK-mediated K + outflow significantly contributes to hippocampal LTP, as well as learning and memory.
Keyphrases
- cognitive impairment
- protein kinase
- cerebral ischemia
- working memory
- high frequency
- induced apoptosis
- adipose tissue
- spinal cord
- multiple sclerosis
- depressive symptoms
- endothelial cells
- cell death
- cell proliferation
- machine learning
- reactive oxygen species
- label free
- insulin resistance
- signaling pathway
- resting state
- data analysis
- sleep quality