Intermittent Hypoxia (IH) modulates the effects of Corticotropin‐Releasing Hormone (CRH) on NTS neuronal synaptic transmission

Abstract

We examined if exposure to IH, a model of the arterial hypoxemia that occurs during sleep apnea, modulates the effects of activation of CRH receptors (CHRRs) on NTS neuronal synaptic transmission. Whole‐cell recordings from NTS second‐order arterial chemoreceptor neurons, identified by DiA labeling of carotid bodies, were obtained in a caudal NTS slices (250μM thick). Slices were incubated with 100nM of the CRHR1 selective agonist stressin I or 100nM of the CRHR2 selective agonist urocortin II in aCSF for 20 minutes and slices studies 0.5–2.0 hrs later. Spontaneous miniature excitatory postsynaptic currents (mEPSCs) and inhibitory postsynaptic currents (mIPSCs) were recorded in separate slices under voltage clamp 0.5–2 hours after the 20min agonist incubation from both normoxic controls and slices obtained from rats exposed to IH for 7 days. The CRHR1 selective agonist and antagonist had no any effect on mEPSC amplitude or frequency. The CRHR2 selective agonist urocortin II significantly increased mEPSC amplitude (21.60 ± 1.03pA, n=13 vs 26.74 ± 1.13pA, n=11, p<0.01) in normoxic rats but did not alter mEPSC frequency. Exposure to IH increased mEPSC amplitude and in IH exposed rats urocortin II prevented the IH‐induced increase in mEPSC amplitude (27.42 ± 1.32pA, n=15 vs 22.35 ± 0.82pA, n=14, p<0.01). On the other hand, the CRHR1 agonist stressin I significantly enhanced mIPSC amplitude in slices from control, normoxic rats (32.57 ± 2.31pA, n=10 vs 38.14 ± 1.4pA, n=12, p<0.05), but neither IH nor stressin I altered mIPSC amplitudes and frequency in slices from IH exposed rats. The CRHR2 agonist did not alter mIPSC frequency or amplitude. In separate experiments, 10min prior to incubation of the slice with the CRHR selective agonist, the slice was pre‐treated with either CRHR1 antagonist NBI35965 (1μM) or CRHR2 antagonist K41498 (100nM). The CRHR2 selective antagonist K41498 attenuated the urocortin II effect on mEPSCs and the CRHR1 antagonist NBI35965 attenuated the stressin 1 effect on mIPSCs. Our findings provide evidence that CRH can modulate NTS neuronal glutamatergic transmission and GABAergic transmission through different CRHR subtypes. After IH, CRHR2 receptor activation reverses IH‐inudced increases in mEPSC amplitude, whereas after IH CRHR1 receptor activation no longer increases mIPSC amplitude. These changes appear to be primarily mediated by alterations in the post‐synaptic neuron.Support or Funding InformationNIH HL088052This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.