کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1942776 | 1052628 | 2010 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Extracellular calcium depletion transiently elevates oxygen consumption in neurosecretory PC12 cells through activation of mitochondrial Na+/Ca2+ exchange Extracellular calcium depletion transiently elevates oxygen consumption in neurosecretory PC12 cells through activation of mitochondrial Na+/Ca2+ exchange](/preview/png/1942776.png)
Fluctuating extracellular Ca2+ regulates many aspects of neuronal (patho)physiology including cell metabolism and respiration. Using fluorescence-based intracellular oxygen sensing technique, we demonstrate that depletion of extracellular Ca2+ from 1.8 to ≤ 0.6 mM by chelation with EGTA induces a marked spike in O2 consumption in differentiated PC12 cells. This respiratory response is associated with the reduction in cytosolic and mitochondrial Ca2+, minor depolarization on the mitochondrial membrane, moderate depolarization of plasma membrane, and no changes in NAD(P)H and ATP. The response is linked to the influx of extracellular Na+ and the subsequent activation of mitochondrial Na+/Ca2+ and Na+/H+ exchange. The mitochondrial Na+/Ca2+ exchanger (mNCX) activated by Na+ influx reduces Ca2+ and increases Na+ levels in the mitochondrial matrix. The excess of Na+ activates the mitochondrial Na+/H+ exchanger (NHE) increasing the outward pumping of protons, electron transport and O2 consumption. Reduction in extracellular Na+ and inhibition of Na+ influx through the receptor operated calcium channels and plasmalemmal NHE reduce the respiratory response. Inhibition of the mNCX, L-type voltage gated Ca2+ channels or the release of Ca2+ from the endoplasmic reticulum also reduces the respiratory spike, indicating that unimpaired intercompartmental Ca2+ exchange is critical for response development.
Journal: Biochimica et Biophysica Acta (BBA) - Bioenergetics - Volume 1797, Issue 9, September 2010, Pages 1627–1637