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Chronic Nicotine Blunts Hypoxic Sensitivity in Perinatal Rat Adrenal Chromaffin Cells via Upregulation of KATP Channels: Role of {alpha}7 Nicotinic Acetylcholine Receptor and Hypoxia-Inducible Factor-2{alpha}  

Fetal nicotine exposure blunts hypoxia-induced catecholamine secretion from neonatal adrenomedullary chromaffin cells (AMCs), providing a link between maternal smoking, abnormal arousal responses, and risk of sudden infant death syndrome. Here, we show that the mechanism is attributable to upregulation of KATP channels via stimulation of {alpha}7 nicotinic ACh receptors (AChRs). These KATP channels open during hypoxia, thereby suppressing membrane excitability. After in utero exposure to chronic nicotine, neonatal AMCs show a blunted hypoxic sensitivity as determined by inhibition of outward K+ current, membrane depolarization, rise in cytosolic Ca2+, and catecholamine secretion. However, hypoxic sensitivity could be unmasked in nicotine-exposed AMCs when glibenclamide, a blocker of KATP channels, was present. Both KATP current density and KATP channel subunit (Kir 6.2) expression were significantly enhanced in nicotine-exposed cells relative to controls.

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