BK channels sustain neuronal Ca2+ oscillations to support hippocampal long-term potentiation and memory formation

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 acqu...

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Published in:Cellular and molecular life sciences : CMLS 2023-12, Vol.80 (12), p.369-369, Article 369
Main Authors: Pham, Thomas, Hussein, Tamara, Calis, Dila, Bischof, Helmut, Skrabak, David, Cruz Santos, Melanie, Maier, Selina, Spähn, David, Kalina, Daniel, Simonsig, Stefanie, Ehinger, Rebekka, Groschup, Bernhard, Knipper, Marlies, Plesnila, Nikolaus, Ruth, Peter, Lukowski, Robert, Matt, Lucas
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biosensors
Brain slice preparation
Calcium channels
Calcium channels (L-type)
Calcium channels (voltage-gated)
Calcium conductance
Calcium ions
Calcium signalling
Cell Biology
Channels
Cognitive ability
Fluorescence
Genetic code
Glutamic acid receptors
Glutamic acid receptors (ionotropic)
Hippocampus
Impairment
Life Sciences
Long-term potentiation
Memory
N-Methyl-D-aspartic acid receptors
Original Article
Potassium
Potassium channels (calcium-gated)
Potassium channels (voltage-gated)
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Summary: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.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-023-05016-y