Postnatal hyperoxia impairs acute oxygen sensing of rat glomus cells by reduced membrane depolarization.
Previous work demonstrated that hyperoxia (30-60% O(2)) exposure in the post-natal period reduces the ventilatory response to acute hypoxia and this impairment may continue considerably beyond the period of hyperoxia exposure. Previous work from our laboratory demonstrated that 1-2 weeks of hyperoxia (60% O(2)) starting between P1 and P14: reduced the single chemoreceptor unit response to hypoxia, reduced the rise in glomus cell calcium caused by acute hypoxia and reduced hypoxia-induced catecholamine release (Donnelly 05, Donnelly 09). The present study asked whether the impairment extended to hypoxia-induced membrane depolarization, an earlier step in the transduction cascade. Perforated patch, whole-cell recordings were obtained from rat glomus cells exposed to hyperoxia from P0-P8 or P8-P15 and age-matched control groups. In both cases, hypoxia-induced membrane depolarization was significantly less in the hyperoxia treated groups compared to controls, while depolarization to 20 mM K(+) was not significantly affected. Resting membrane potential and input resistance were also not different in the hyperoxia treated groups. Whole carotid body quantitative real time PCR showed that TASK-1, TASK-3 and L-type Ca(2+) channel expression was significantly down-regulated at Hyper 8-15 compared to controls. We conclude that 1 week of postnatal hyperoxia during the early and late stage of CB maturation impairs organ function by affecting the coupling between hypoxia and glomus cell depolarization. This may be caused by altered expression of TASK1, TASK3 or L-type Ca(2+) channel gene expression. We speculate that an identification of cellular changes caused by hyperoxia may yield unique insights to the mechanism of oxygen sensing by the carotid bodies.
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. kiminsook@uams.edu
Insook
I
Kim
David F
DF
Donnelly
John L
JL
Carroll
D000818:Animals; D002344:Carotid Body / Q000166:cytology / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D018496:Hyperoxia / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010100:Oxygen