Chronic nicotine in utero and in vitro abrogates O2‐sensitivity in perinatal rat adrenomedullary chromaffin cells

Rat adrenomedullary chromaffin cells (AMC) possess an O2‐sensing mechanism that is critical for the neonate to survive hypoxic stress. This mechanism promotes catecholamine secretion during hypoxia and is lost postnatally as AMC acquire sympathetic cholinergic innervation. Here, we tested the hypothesis that activation of nicotinic ACh receptors (AChR) in rat AMC is a critical step leading to the loss of O2‐ sensitivity, indicated by the absence of: hypoxic inhibition of outward K+ current and membrane depolarization in whole‐cell recordings; hypoxia‐induced increase in ATP secretion using luciferin‐luciferase chemiluminescence; and hypoxia‐induced increase in intracellular Ca2+ using fura‐2. Interestingly, precocious activation of nicotinic AChR in utero, via maternal administration of chronic nicotine (1 mg/Kg body weight/day), led to the abrogation of hypoxic sensitivity in neonatal AMC; in contrast, saline‐treated controls showed normal hypoxic responses. Similarly, when neonatal rat AMC were cultured for ~ 7days in the presence of nicotine (100 μM) hypoxic sensitivity was largely absent, in contrast to control cells grown without nicotine. Additionally, the majority of juvenile AMC, which lack O2 sensitivity soon after isolation, re‐acquired hypoxic sensitivity when kept ‘functionally‐denervated’ in culture for ~ 7 days. These data strongly suggest that activation of nicotinic AChR is a key regulator of O2‐ sensitivity in AMC, and moreover, provide a link between maternal exposure to cigarette smoke and neonatal morbidity. Supported by grants from HSFO1, and CIHR2.