Potential Role of Mitochondria in Hypoxia Sensing by Adrenomedullary Chromaffin Cells

Exposure of the neonate to episodes of acute hypoxia during birth results in a variety of adaptive changes that include fluid re-absorption and secretion of surfactant in the lungs to promote air breathing (Slotkin and Seidler 1988). These physiological responses depend critically on catecholamine secretion from adrenomedullary chromaffin cells (AMC), which express a direct, developmentally-regulated hypoxia sensing mechanism, independent of the nervous system (Slotkin and Seidler 1988, 1986; Thompson et al., 1997). The hypoxic response in neonatal AMC, as well as their immortalized counterparts (i.e. MAH cells), appears to be mediated via inhibition of O2-sensitive K+ channels, though the signaling pathway is not completely understood (Fearon et al 2002; Thompson et al., 1997). These O2 -sensitive K+ channels include large conductance Ca2+-dependent K+, i.e. BK or maxi-K+, and delayed rectifier K+ channels (Thompson and Nurse 1998; Thompson et al., 2002). Inhibition of these channels is thought to facilitate membrane depolarization, voltage-gated Ca2+ entry and catecholamine secretion (Thompson et al., 1997; Thompson and Nurse, 1998, 2000).