Sodium Cyanide And Hypoxic Hypoxia Similarly Excite PreBötzinger Complex Neurons In Neonatal Rat Transverse Medullary Slice

Abstract

Recent work from our laboratory showed that, in the in vitro transverse medullary slice preparation containing the preBötzinger complex (pBc), sodium cyanide (NaCN) elicits an increase in hypoglossal (XII) motor output similar to that seen in response to severe hypoxia. However, we do not yet know whether pBc neuronal activity is similarly increased by NaCN and severe hypoxia. To assess this, Ca2+-sensitive fluorescent dyes and whole-cell current-clamp recording techniques were used to examine pBc population and single cell activities in response to focal pBc NaCN (5 or 10mM, 2–5nl), bath application of NaCN (200μM) or hypoxic hypoxia (94% N2/1% O2/5% CO2) in neonatal rat (P1–P4) slice preparations (n=7). Focal or bath applied NaCN and hypoxic hypoxia increased fluorescence intensity (ΔF/F) in a subset of rhythmically-active labeled pBc neurons and, in some cases, progressed to tonic activity in the pBc. ΔF/F returned to baseline levels following cessation of NaCN application. Focal pBc NaCN application also elicited an increase in neuronal activity that persisted beyond the duration of NaCN ejection, although activity returned to baseline levels after a brief recovery period. Our results suggest that NaCN mimics hypoxic hypoxia effects on pBc neuronal activity in slices; providing additional support for intrinsic hypoxic chemosensitivity in the pBc. Supported by HL62527, HL63175