The hypoxia‐sensitivity of RVLM sympathetic premotor neurons is mediated by glial ATP release (1130.1)

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.