Developmental loss of hypoxic chemosensitivity in rat adrenomedullary chromaffin cells.

Abstract

1. We investigated whether adrenomedullary chromaffin cells (AMCs) derived from neonatal (postnatal day (P) 1‐P2) and juvenile (P13‐P20) rats, and maintained in short‐term culture (1‐3 days), express O2‐chemoreceptive properties. 2. In whole‐cell recordings, the majority (approximately 70%; n = 47) of neonatal AMCs were sensitive to hypoxia. Under voltage clamp, acute hypoxia (PO2 approximately 40 mmHg) suppressed voltage‐dependent K+ current by 25.1 +/‐ 3.4% (mean +/‐ S.E.M.; n = 22); under current clamp, acute hypoxia caused a membrane depolarization of 14.1 +/‐ 1.3 mV (n = 13) from a resting potential of ‐54.8 +/‐ 2.8 mV (n = 13), and this was often sufficient to trigger action potentials. 3. Exposure of neonatal AMC cultures to a moderate (PO2 approximately 75 mmHg) or severe (PO2 approximately 35 mmHg) hypoxia for 1 h caused a dose‐dependent stimulation (approximately 3 or 6 times normoxia, respectively) of catecholamine (CA) release, mainly adrenaline, determined by HPLC. This induced CA release was abolished by the L‐type calcium channel blocker, nifedipine (10 microM). 4. In contrast to the above results in neonates, hypoxia had no significant effects on voltage‐dependent K+ current, membrane potential, or CA release in juvenile AMCs. 5. We conclude that rat adrenal chromaffin cells possess a developmentally regulated O2‐sensing mechanism, similar to carotid body type I cells.