ϩ currents that inhibit hypoxia-induced depolarization and that a decrease in this current with age could underlie, in part, the developmental increase in type I cell depolarization response to hypoxia. In dissociated type I cells from 0-to 1-and 11-to 16-day-old rats, using perforated patch-clamp and 70 mM K ϩ extracellular solution, we measured repolarization-induced inward K ϩ tail currents in the absence and presence of E-4031, a specific HERG channel blocker. This allowed isolation of the E-4031-sensitive HERG-like current. E-4031-sensitive peak currents in type I cells from 0-to-1-day-old rats were 2.5-fold larger than in cells from 11-to 16-day-old rats. E-4031-sensitive current density in newborn type I cells was twofold greater than in cells from 11-to 16-day-old rats. Under current clamp conditions, E-4031 enhanced hypoxia-induced depolarization in type I cells from 0-to-1-day-old but not 11-to 16-day-old rats. With use of fura 2 to measure intracellular Ca 2ϩ , E-4031 increased the cytosolic Ca 2ϩ concentration response to anoxia in cells from 0-to-1-day-old but not cells from 11-to 16-day-old rats. E-4031-sensitive K ϩ currents are present in newborn carotid body type I cells and decline with age. These findings are consistent with a role for E-4031-sensitive K ϩ current, and possibly HERG-like K ϩ currents, in the type I cell hypoxia response maturation.human ether-a-go-go-related gene; potassium channel; hypoxia THE CAROTID BODY chemoreceptors mediate ventilatory and other defensive responses to hypoxic stress in mammals (11,23,28) and appear to be important for survival during postnatal maturation (14,21,28). Despite their importance, the carotid chemoreceptors in neonates exhibit low sensitivity to hypoxia compared with adults and become more sensitive over the first few weeks of life. This process, termed "resetting" of carotid body O 2 sensitivity, occurs in all mammalian species studied to date (8,9,12,20,29,36,37