Journal Article

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

2023

Overview

Mutations of large conductance Ca2+- 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 Ca2+-sensitive probe to observe cultured hippocampal neurons during chemical LTP (cLTP) induction. cLTP massively reduced intracellular K+ concentration ([K+]i) while elevating L-Type Ca2+ channel- and NMDA receptor-dependent Ca2+ oscillation frequencies. Both, [K+]i decrease and Ca2+ 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.

• Publisher: Springer Nature B.V
• Subject: Biosensors / Brain slice preparation / Calcium channels / Calcium channels (L-type) / Calcium channels (voltage-gated) / Calcium conductance / Calcium ions / Calcium signalling / Channels / Cognitive ability / Fluorescence / Genetic code / Glutamate receptors / Glutamic acid receptors (ionotropic) / Hippocampus / Impairment / Long-term potentiation / Memory / N-Methyl-D-aspartic acid receptors / Potassium / Potassium channels (calcium-gated) / Potassium channels (voltage-gated)