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

Benjamin Gaston; Walter J May; Spencer Sullivan; Sean Yemen; Nadzeya V Marozkina; Lisa A Palmer; James N Bates; Stephen J Lewis

doi:10.1152/japplphysiol.01050.2013

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

Journal article

Open access

Peer reviewed

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

Benjamin Gaston, Walter J May, Spencer Sullivan, Sean Yemen, Nadzeya V Marozkina, Lisa A Palmer, James N Bates and Stephen J Lewis

Journal of applied physiology (1985), Vol.116(10), pp.1290-1299

05/15/2014

DOI: 10.1152/japplphysiol.01050.2013

PMCID: PMC4044395

PMID: 24610531

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Abstract

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, and in the 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 on the Bchain (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 an essential role in mediating carotid sinus nerve-dependent short-term potentiation, an important mechanism for recovery from acute hypoxia.

Consciousness

Pulmonary Ventilation

Mice, Inbred C57BL

Hemoglobins - metabolism

Male

Mice, Transgenic

Structure-Activity Relationship

Cysteine - chemistry

Carotid Sinus - physiopathology

Hemoglobins - chemistry

Animals

Hypoxia - physiopathology

Cysteine - metabolism

Mice

Respiratory Mechanics

Details

Title: Subtitle: Essential role of hemoglobin beta-93-cysteine in posthypoxia facilitation of breathing in conscious mice
Creators: Benjamin Gaston - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia; bmg46@case.edu
Walter J May - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia
Spencer Sullivan - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia
Sean Yemen - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia
Nadzeya V Marozkina - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia
Lisa A Palmer - Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia
James N Bates - Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, Iowa; and
Stephen J Lewis - Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, Ohio
Resource Type: Journal article
Publication Details: Journal of applied physiology (1985), Vol.116(10), pp.1290-1299
DOI: 10.1152/japplphysiol.01050.2013
PMID: 24610531
PMCID: PMC4044395
NLM abbreviation: J Appl Physiol (1985)
ISSN: 8750-7587
eISSN: 1522-1601
Publisher: United States
Grant note: P01 HL101871 / NHLBI NIH HHS R01-HL-59337 / NHLBI NIH HHS 1P-01-HL-101871 / NHLBI NIH HHS U10 HL109250 / NHLBI NIH HHS
Language: English
Date published: 05/15/2014
Academic Unit: Anesthesia
Record Identifier: 9984007157302771

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