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Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells

¹Division of Pediatric Pulmonology, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, and Children's Hospital Research Institute; and ²Arkansas Children's Hospital, Little Rock, Arkansas

Submitted 24 November 2003 ; accepted in final form 28 November 2004

The O₂ sensitivity of dissociated type I cells from rat carotid body increases with age until 14–16 days. Hypoxia-induced depolarization appears to be mediated by an O₂-sensitive K⁺ current, but other K⁺ currents may modulate depolarization. We hypothesized that membrane potential may be stabilized in newborn type I cells by human ether-a-go-go-related gene (HERG)-like K⁺ 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⁺ extracellular solution, we measured repolarization-induced inward K⁺ 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 Ca²⁺, E-4031 increased the cytosolic Ca²⁺ 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⁺ 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⁺ current, and possibly HERG-like K⁺ currents, in the type I cell hypoxia response maturation.

human ether-a-go-go-related gene; potassium channel; hypoxia

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