US EPA

2252383 

Journal Article 

Essential role of hemoglobin beta-93-cysteine in post-hypoxia facilitation of breathing in conscious mice 

Gaston, B; May, WJ; Sullivan, S; Yemen, S; Marozkina, NV; Palmer, LA; Bates, JN; Lewis, SJ 

2014 

Yes 

Journal of Applied Physiology (1985)
ISSN: 8750-7587
EISSN: 1522-1601 

116 

10 

1290-1299 

English 

24610531 

10.1152/japplphysiol.01050.2013 

WOS:000339167900005 

When erythrocyte hemoglobin (Hb) is fully saturated with O2, nitric oxide (NO) covalently binds to the cysteine 93 residue of the Hb β-chain (B93-CYS) forming S-nitrosohemoglobin . Binding of NO is allosterically coupled to the O2 saturation of Hb. As saturation falls, the NO group on B93-CYS is transferred to thiols in the erythrocyte membrane and cytosol, and in plasma, forming circulating S-nitrosothiols. Here, we studied whether the changes in ventilation during and following exposure to a hypoxic challenge were dependent on erythrocytic B93-CYS. Studies were performed in conscious mice in which native murine Hb was replaced with human Hb (hB93-CYS mice) and in mice in which murine Hb was replaced with human Hb containing an alanine rather than cysteine at position 93 (hB93-ALA). Both strains expressed human γ-chain Hb, likely allowing a residual element of S-nitrosothiol-dependent signaling. While resting parameters and initial hypoxic (10% O2, 90% N2) ventilatory responses were similar in hB93-CYS mice and hB93-ALA mice, the excitatory ventilatory responses (short-term potentiation) that occurred once the mice were returned to room-air were markedly diminished in hB93-ALA mice. Further, short-term potentiation responses were virtually absent in mice with bilateral transection of the carotid sinus nerves. These data demonstrate that hB93-CYS plays a key role in mediating carotid sinus nerve-dependent short-term potentiation, an important mechanism for recovery from acute hypoxia. 

hemoglobin; S-nitrosothiol; S-nitrosylation; ventilation; hypoxia; posthypoxia