Premium
NADPH oxidase activity is necessary for acute intermittent hypoxia‐induced phrenic long‐term facilitation
Author(s) -
MacFarlane P. M.,
Satriotomo I.,
Windelborn J. A.,
Mitchell G. S.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.165597
Subject(s) - nadph oxidase , phrenic nerve , apocynin , spinal cord , cytosol , hypoxia (environmental) , synaptic plasticity , chemistry , biology , reactive oxygen species , microbiology and biotechnology , pharmacology , neuroscience , respiratory system , biochemistry , anatomy , oxygen , receptor , enzyme , organic chemistry
Phrenic long‐term facilitation (pLTF) following acute intermittent hypoxia (AIH) is a form of spinal, serotonin‐dependent synaptic plasticity that requires reactive oxygen species (ROS) formation. We tested the hypothesis that spinal NADPH oxidase activity is a necessary source of ROS for pLTF. Sixty minutes post‐AIH (three 5‐min episodes of 11% O 2 , 5 min intervals), integrated phrenic and hypoglossal (XII) nerve burst amplitudes were increased from baseline, indicative of phrenic and XII LTF. Intrathecal injections (∼C 4 ) of apocynin or diphenyleneiodonium chloride (DPI), two structurally and functionally distinct inhibitors of the NADPH oxidase complex, attenuated phrenic, but not XII, LTF. Immunoblots from soluble (cytosolic) and particulate (membrane) fractions of ventral C 4 spinal segments revealed predominantly membrane localization of the NADPH oxidase catalytic subunit, gp91 phox , whereas membrane and cytosolic expression were both observed for the regulatory subunits, p47 phox and RAC1. Immunohistochemical analysis of fixed tissues revealed these same subunits in presumptive phrenic motoneurons of the C 4 ventral horn, but not in neighbouring astrocytes or microglia. Collectively, these data demonstrate that NADPH oxidase subunits localized within presumptive phrenic motoneurons are a major source of ROS necessary for AIH‐induced pLTF. Thus, NADPH oxidase activity is a key regulator of spinal synaptic plasticity, and may be a useful pharmaceutical target in developing therapeutic strategies for respiratory insufficiency in patients with, for example, cervical spinal injury.