Enhanced Phrenic Long‐Term Facilitation Following Repetitive Acute Intermittent Hypoxia: Role of Glycolytic Flux

Abstract

Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as phrenic long‐term facilitation (pLTF). pLTF is enhanced by pre‐treatment with repetitive AIH (3xwAIH: 10.5% O2; 10, 5min episodes/day, 3 days/week for 4 weeks; Vinit et al. ibid), and this enhancement (metaplasticity) is associated with increased expression of key molecules necessary for pLTF (Satriotomo et al. ibid). Since cell glycolysis affects transcriptional regulation of the same key molecules (Carriga‐Canut et al. 2006), we tested the hypothesis that the glycolytic inhibitor 2‐deoxyglucose (2‐DG) prevents the metaplasticity associated with pLTF following 3xwAIH. In anesthetized rats, phrenic nerve activity was increased (ie. pLTF 47%, p<0.05) 60min post‐AIH (3, 5min episodes, 10.5% O2) and this was enhanced by pre‐treatment with 3xwAIH (110%, p<0.05). Further, the enhanced pLTF was prevented in rats that also received 2‐DG in their drinking water (80mg/kg/day) during 3xwAIH, but similar to normoxic‐treated rats (50%). Acute 2‐DG administration (240mg/kg i.p.) had no effect on pLTF indicating glycolytic flux is necessary for the metaplasticity underlying 3xwAIH‐induced pLTF. Our data suggest a novel link between glycolysis and pLTF induced by repetitive AIH and that genes regulating respiratory metaplasticity may be linked to cellular energy metabolism (NIH HL‐80209 and Francis Family Foundation).