Near-infrared light activates mitochondrial potassium channels and triggers neuroprotection in hippocampal neurons
Researchers have shown that 820 nm near-infrared light activates mitochondrial large-conductance calcium-activated potassium (mitoBKCa) channels in rat hippocampal mitochondria and provides neuroprotection in NMDA-damaged brain tissue cultures. The study, using patch-clamp electrophysiology, CRISPR/Cas9 gene editing, and transcriptomic analysis, identifies both an acute channel-activation response and a longer-term gene expression remodeling effect. The findings help clarify the molecular mechanisms behind photobiomodulation, a light-based therapy with potential applications in neurological disease treatment and prevention.
A new preprint study on bioRxiv investigated how near-infrared (NIR) light at 820 nm exerts its reported neuroprotective effects, focusing on mitochondrial potassium channels. Using patch-clamp recordings, the researchers demonstrated that 820 nm illumination directly activates mitoBKCa channels in mitochondria isolated from rat hippocampal tissue, and that this illumination also conferred neuroprotection in organotypic hippocampal cultures exposed to NMDA, a model of excitotoxic injury. The same channel activation was observed in human glioma U-87 MG cell mitochondria, broadening the relevance of the finding beyond rodent models. To probe the channel's specific role, the team used CRISPR/Cas9 to generate U-87 MG cells lacking the BKCa channel α-subunit, then compared transcriptomes of illuminated wild-type and knockout cells, revealing substantial differences in gene expression. The study proposes two distinct mechanisms: an acute cytoprotective effect mediated by mitoBKCa channel activation, and a long-term effect involving widespread transcriptome remodeling. The primary photoacceptor is thought to be cytochrome c oxidase, whose copper centers absorb light in the red and NIR range near 820 nm. Together, these findings advance the mechanistic understanding of photobiomodulation and may inform optimization of light-based neurological therapies.
What's missing
As a preprint, this study has not yet undergone peer review. Key limitations include the use of isolated mitochondria and cell culture models rather than in vivo systems, leaving open questions about whether these mechanisms operate similarly in intact living organisms. The study does not establish dose-response relationships for therapeutic NIR light exposure, and the functional significance of the transcriptomic changes identified in CRISPR knockout cells remains to be characterized. It is also unclear whether the neuroprotective effects observed translate to clinically relevant light delivery parameters.
What different sources said
- bioRxivCenter
Near-infra red light and mitochondrial large-conductance calcium-activated potassium channels: protection of hippocampal neurons, influence on channel activity and transcriptome remodelling
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