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.
|Number of pages||1|
|Publication status||Published - Apr 2014|