In neurons, excitotoxic stimulation induces mitochondrial calcium overload and the release of pro-apoptotic proteins, which triggers delayed cell death. The precise mechanisms of apoptogen release, however, remain controversial. To characterize the linkage between mitochondrial calcium load and cell vulnerability, and to test the hypothesis that only a subpopulation of mitochondria damaged by c...

Nociceptive neurons play an important role in ischemia by sensing and transmitting information to the CNS and by secreting peptides and nitric oxide, which can have local effects. While these responses are probably primarily mediated by acid sensing channels, other events occurring in ischemia may also influence neuron function. In this study, we have investigated the effects of anoxia and anox...

The hepatic uptake of quinine, fluvoxamine, and fluoxetine (0.1-10 microM) was investigated with freshly isolated rat hepatocytes. The cell-to-medium concentration ratios (K(p)) were concentration-dependent: the mean maximum K(p) values (at 0.1 microM) were 150 (quinine), 500 (fluvoxamine), and 2000 (fluoxetine). There was also a large capacity site that was not saturable over the concentration...

The temporal relationship between mitochondrial membrane permeabilization and reactive oxygen species production during apoptosis remains unknown. We analyzed the rate of superoxide production of human breast carcinoma cells expressing a cytochrome c-green fluorescent protein (cyt-c-GFP) fusion protein at the single-cell level during apoptosis. In cells treated with the proapoptotic agents stau...

We have used digital fluorescence imaging techniques to explore the interplay between mitochondrial Ca 2 1 uptake and physiological Ca 2 1 signaling in rat cortical astrocytes. A rise in cytosolic Ca 2 1 ([Ca 2 1 ] cyt ), resulting from mobilization of ER Ca 2 1 stores was followed by a rise in mitochondrial Ca 2 1 ([Ca 2 1 ] m , monitored using rhod-2). Whereas [Ca 2 1 ] cyt recovered within z...

Recent studies have suggested that mitochondria may play important roles in the Ca(2+) homeostasis of cardiac myocytes. However, it is still unclear if mitochondrial Ca(2+) flux can regulate the generation of Ca(2+) waves (CaWs) and triggered activities in cardiac myocytes. In the present study, intracellular/cytosolic Ca(2+) (Cai (2+)) was imaged in Fluo-4-AM loaded mouse ventricular myocytes....

Several lines of evidence suggest that neuronal mitochondria accumulate calcium when the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) is elevated to levels approaching approximately 500 nM, but the spatial, temporal, and quantitative characteristics of net mitochondrial Ca uptake during stimulus-evoked [Ca(2+)](i) elevations are not well understood. Here, we report direct measurements of d...

We have used an aequorin chimera targeted to the membrane of the secretory granules to monitor the free [Ca(2+)] inside them in neurosecretory PC12 cells. More than 95% of the probe was located in a compartment with an homogeneous [Ca(2+)] around 40 microM. Cell stimulation with either ATP, caffeine or high-K(+) depolarization increased cytosolic [Ca(2+)] and decreased secretory granule [Ca(2+)...

Geiger JE, Magoski NS. Ca -induced Ca release in Aplysia bag cell neurons requires interaction between mitochondrial and endoplasmic reticulum stores. J Neurophysiol 100: 24–37, 2008. First published May 7, 2008; doi:10.1152/jn.90356.2008. Intracellular Ca is influenced by both Ca influx and release. We examined intracellular Ca following action potential firing in the bag cell neurons of Aplys...

In cells, such as neurones and immune cells, mitochondria can form dynamic and extensive networks that change over the minute timescale. In contrast, mitochondria in adult mammalian skeletal muscle fibres show little motility over several hours. Here, we use a novel three channelled microflow device, the multifunctional pipette, to test whether mitochondria in mouse skeletal muscle connect to e...