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Bednarczyk, P.

Publications and source records attributed to Bednarczyk, P..

4 recordsLinked to original sources

Infrared light stimulates the mitochondrial large-conductance calcium-activated potassium channel in guinea pig cardiomyocytes.

Mitochondrial potassium channels play an important role in regulating cellular metabolism, redox balance, and survival, particularly in excitable tissues such as the heart. Among them, the mitochondrial large-conductance calcium-activated potassium (mitoBKCa) channel has been implicated in cardioprotection during ischemia-reperfusion injury. At the same time, growing evidence indicates that mitochondria act as light responsive organelles, with cytochrome c oxidase (COX) serving as a primary chromophore for red and near-infrared (NIR) light. In this study, we investigated whether 820 nm infrared light modulates mitoBKCa channel activity in mitochondria isolated from guinea pig cardiomyocytes. Using patch-clamp recordings of mitoplasts, we demonstrated that illumination at 820 nm NIR wavelength enhanced mitoBKCa channel activity in a redox-dependent manner. Our findings reveal a previously unrecognized mechanism linking NIR light modulation via COX to the regulation of cardiac mitoBKCa channels as a metabolic sensor. This study identifies the mitoBKCa channel as a novel effector of light-induced mitochondrial signaling and suggests that modulation of cardiac mitochondrial potassium transport by NIR light may contribute to cardioprotective effects. These results provide new insight into the integration of bioenergetic and photoregulatory processes in mitochondria and support the development of non-pharmacological strategies targeting mitochondrial function.

biochemistry↗

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

neuroscience↗

Red/near-infrared light activates the mitochondrial large-conductance calcium-activated potassium channel in glioblastoma cells.

Mitochondrial potassium channels, located in the inner mitochondrial membrane, play a crucial role in the cells life/death phenomenon. Activation of mitochondrial potassium channels by potassium channel openers may protect cells against ischemia-reperfusion injury. It is known that mitochondrial large conductance calcium-activated potassium channels interact with various mitochondrial proteins, including enzymes of the respiratory chain. Numerous studies indicate that the mitochondria, especially cytochrome c oxidase, play a crucial role as a chromatophore in the cellular response to red and near-infrared light. In this study, we employ the patch-clamp technique and single-channel recordings to investigate the regulation of glioblastoma mitochondrial large conductance calcium-activated potassium channel activity by infrared light. Specifically, we examined the effects of wavelengths 620 nm, 680 nm, 760 nm, and 820 nm in a redox-controlled environment. Our findings suggest that illuminating the inner mitochondrial membrane with these wavelengths may activate mitochondrial large conductance calcium-activated potassium channels. These results offer new insights into the regulation of mitochondrial potassium channels by cytochrome c oxidase, which may lead to the development of non-pharmacological interventions with potential cytoprotective benefits.

biochemistry↗

mitoBKCa is functionally expressed in murine and human breast cancer cells and promotes metabolic reprogramming

Alterations in the function of K+ channels such as the voltage- and Ca2+ activated K+ channel of large conductance (BKCa) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BKCa splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBKCa). Through a combination of genetic knockdown and knockout along with cell permeable BKCa channel blocker, we show that mitoBKCa modulates overall cellular and mitochondrial energy production and mediates the metabolic rewiring referred to as the "Warburg effect", thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBKCa and BKCa transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBKCa could represent a treatment strategy for selected BC patients in future.

cancer biology↗