Cheng 2008 Cell Physiol Biochem
| Cheng Y, Gu XQ, Bednarczyk P, Wiedemann FR, Haddad GG, Siemen D (2008) Hypoxia increases activity of the BK-channel in the inner mitochondrial membrane and reduces activity of the permeability transition pore. Cell Physiol. Biochem. 22: 127-136. |
» [[Has info::PMID: 18769039]]
Cheng Y, Gu XQ, Bednarczyk P, Wiedemann FR, Haddad GG, Siemen D (2008) Cell Physiol. Biochem.
Abstract: Hypoxia can cause severe damage to cells by initiating signaling cascades that lead to cell death. A cellular oxygen sensor, other than the respiratory chain, might exist in sensitive components of these signaling cascades. Recently, we found evidence that mitochondrial ion channels are sensitive to low levels of oxygen. We therefore studied the effects of hypoxia on the mitochondrial BK-channel (mtBK), on the mitochondrial permeability transition pore (PTP), and on their possible interaction. Using single-channel patch-clamp techniques we found that hypoxia inhibited the PTP but substantially increased the mtBK activity of mitoplasts from rat liver and astrocytes. Experiments measuring the mitochondrial membrane potential of intact rat brain mitochondria (using the fluorescence dye safranine O) during hypoxia exhibited an increased Ca(2+)-retention capacity implying an impaired opening of the PTP. We also found a reduced Ca(2+)-retention capacity with 100 nM iberiotoxin, a selective inhibitor of BK-channels. We therefore conclude that there is interaction between the mtBK and the PTP in a way that an open mtBK keeps the PTP closed. Thus, the response of mitochondrial ion channels to hypoxia could be interpreted as anti-apoptotic. • Keywords: BK-channel, Permeability transition pore, Hypoxia, Inner mitochondrial membrane, Mitochondrial membrane potential
Labels:
Stress:Hypoxia, Ischemia-Reperfusion; Preservation Organism: Rat Tissue;cell: Neurons; Brain, Hepatocyte; Liver Preparation: Intact Cell; Cultured; Primary, Isolated Mitochondria Enzyme: Inner mtMembrane Transporter Regulation: Respiration; OXPHOS; ETS Capacity, Coupling; Membrane Potential, Ion Homeostasis
HRR: Oxygraph-2k
