| 18234847 |
Buttigieg J, Brown ST, Lowe M, Zhang M, Nurse CA: Functional mitochondria are required for O2 but not CO2 sensing in immortalized adrenomedullary chromaffin cells. Am J Physiol Cell Physiol. 2008 Apr;294(4):C945-56. Epub 2008 Jan 30.
Catecholamine (CAT) release from adrenomedullary chromaffin cells (AMC) in response to stressors such as low O (2) (hypoxia) and elevated CO (2)/H (+) is critical during adaptation of the newborn to extrauterine life. Using a surrogate model based on a v-myc immortalized adrenal chromaffin cell line (i.e., MAH cells), combined with genetic perturbation of mitochondrial function, we tested the hypothesis that functional mitochondria are required for O (2) sensing. Wild-type MAH cells responded to both hypoxia and increased CO (2) (hypercapnia) with K (+) current inhibition and membrane depolarization. Additionally, these stimuli caused a rise in cytosolic Ca (2+) and CAT secretion, determined by fura-2 spectrofluorimetry and carbon fiber amperometry, respectively. In contrast, mitochondria-deficient (rho (0)) MAH cells were hypoxia insensitive, although responses to hypercapnia and expression of several markers, including carbonic anhydrase II, remained intact. Rotenone (1 microM), a mitochondrial complex I blocker known to mimic and occlude the effects of hypoxia in primary AMC, was effective in wild-type but not rho (0) MAH cells. These data demonstrate that functional mitochondria are involved in hypoxia-sensing by adrenal chromaffin cells. We also show for the first time that, like their neonatal chromaffin cell counterparts, MAH cells are CO (2) sensors; however, this property is independent of functional mitochondria. |
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