The hypoxia-sensitivity of RVLM sympathetic premotor neurons is mediated by glial ATP release

Lama Bou Farah, Simon McMullan

    Research output: Contribution to journalMeeting abstract

    Abstract

    Sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM) are excited by hypoxia, but the molecular mechanisms of oxygen sensing are unknown. Here we consider two mediators of hypoxia sensing: expression of the oxygen sensing molecule heme oxygenase 2 (HO-2) and glia ATP release. We examined the distribution of HO-2 immunoreactivity in bulbospinal and catecholaminergic brainstem neurons in adult (n = 3) and neonatal (n = 2) rats. Whole cell responses of bulbospinal neurons to acute hypoxia (sodium cyanide, NaCN, 5, 10 or 20 mM) were recorded in acute brainstem slices before and after blockade of HO-2 (SnPP-IX, 10 μM) or ATP receptors (PPADS, 30 μM) and in a specific glial toxin (Fluoroacetate, 5 mM). NaCN caused dose dependent inward currents that were greater in bulbospinal (n = 27) compared to non bulbospinal neurons (1029 ± 316 vs. 169 ± 43 pA at 20 mM NaCN, P < 0.01, n = 12). Responses were unaffected by synaptic (TTX 10 μM, I = -13 ± 12%, P > 0.05, n = 5) or HO-2 blockade (ΔI = 16 ± 26%, P > 0.05, n = 5). HO-2 immunoreactivity was absent in catecholaminergic and bulbospinal neurons and in 12 hypoxia sensitive biocytin filled bulbospinal neurons. Responses to NaCN were reduced by ATP receptor blockade (ΔI = -51± 13%, P < 0.01, n = 6) and abolished by gliocide (20.6 ± 7.7 pA at 20 mM NaCN, n = 12, P < 0.001). These data suggest a crucial role for RVLM glia, not HO-2, in driving sympathetic responses to hypoxia.
    Original languageEnglish
    Article number1130.1
    Pages (from-to)1-1
    Number of pages1
    JournalFASEB Journal
    Volume28
    Issue number1
    Publication statusPublished - Apr 2014

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