Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells.
The O2 sensitivity of dissociated type I cells from rat carotid body increases with age until approximately 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.
Kim
Insook
I
Pediatric Pulmonary Division, Arkansas Children's Hospital, Slot 512-17, 800 Marshall St., Little Rock, AR 72202, USA.
Boyle
Kathleen M
KM
Carroll
John L
JL
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002344:Carotid Body / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010880:Piperidines; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; C063968:E 4031; D011188:Potassium