Near-infra red light and mitochondrial large-conductance calcium-activated potassium channels: protection of hippocampal neurons, influence on channel activity and transcriptome remodelling
Photobiomodulation (PBM) is a therapeutic approach based on illumination with red or near-infrared (NIR) light. Cytochrome c oxidase (COX), a terminal enzyme of the mitochondrial respiratory chain, contains copper centers (CuA and CuB) that absorb light within the red and NIR spectral range, making it a potential primary photoacceptor at wavelengths around 820 nm. PBM appears to be a promising strategy for the treatment and prevention of neurological disorders. Elucidating its precise molecular mechanisms may help optimize therapeutic outcomes. Using patch-clamp method, we showed that illumination with 820 nm light activates mitochondrial large-conductance calcium-activated potassium (mitoBKCa) channels in rat hippocampal mitochondria. Moreover, 820 nm light caused neuroprotective effect in NMDA-treated organotypic hippocampal cultures. Consistently, activation of mitoBKCa channel by 820 nm light illumination was observed in mitochondria isolated from glioma U-87 MG cells. To further investigate the role of mitoBKCa channel, we used CRISPR/Cas9- developed U-87 MG cells lacking the -subunit of the BKCa channel (dBK cells). Comparative transcriptomic analysis of illuminated wild-type and dBK cells revealed significant differences in gene expression profiles. In summary, our results show two types of cellular responses to the PBM. An acute effect involving activation of the mitoBKCa channel and a long-term effect associated with extensive transcriptome remodeling. Both mechanisms may contribute to the cytoprotective effect of 820 nm near-infrared light. HighlightsO_LI820 nm light activates hippocampal mitochondrial BKCa channels C_LIO_LI820 nm light induces hippocampal neuroprotection under excitotoxic conditions C_LIO_LI820 nm light causes intensive transcriptome remodeling in glioma cells C_LIO_LIBKCa channels modulate a subset of transcriptomic responses to 820 nm light C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/731043v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@5a5595org.highwire.dtl.DTLVardef@a8ddb2org.highwire.dtl.DTLVardef@72ec20org.highwire.dtl.DTLVardef@ec46da_HPS_FORMAT_FIGEXP M_FIG C_FIG