Hemoglobin, the oxygen-carrying component of red blood cells, is known as a nitric
oxide (NO) chelating agent. For this reason, hemoglobin has been used widely in
studying the role of nitric oxide in long-term potentiation (LTP) and excitotoxicity.
However, the direct electrophysiological actions of hemoglobin has not been examined.
In this investigation, the actions of hemoglobin on rat hippocampal CAl neurons were
studied since hemoglobin may be present in hemorrhagic stroke and other head injuries.
Superfusion of rat hippocampal slices with 0.1 mM of bovine hemoglobin for 15 minutes
was induced a significant depolarization associated with an increase in the input
resistance. In addition, hemoglobin suppressed the evoked synaptic responses and
increased the depolarization-induced discharge of action potentials, of rat hippocampal
CAl neurons. These hemoglobin-mediated changes usually recovered partially 30
minutes after the removal of hemoglobin.
While the depolarizing action of hemoglobin was enhanced in a calcium-free
medium, it was not significantly changed by 2-amino-5-phosphonovalerate (APV) and 6-
cyano-7-nitroquinoxaline-2,3-dione (CNQX). These observations suggest that the
depolarizing action of hemoglobin is independent of the presence of extracellular calcium
and activations of the excitatory amino acid receptors. Because hemoglobin has been
observed to suppress the depolarizing action of glutamate, it is possible that hemoglobin
suppresses the EPSP by interfering with the actions of glutamate. Although hemoglobin
has been suggested to suppress LTP and excitability by scavenging nitric oxide
(Garthwaite et al., 1988; Haley et al., 1992; 0’ Dell et al., 1991; Schuman and Madison,
1991), the reported actions of hemoglobin were not removed by pre-treatment with 100
pM or 500 pM of No-nitro-L-arginine, a nitric oxide synthase inhibitor. Similar to the scavenging property of hemoglobin, the iron content of hemoglobin probably did not
contribute to the actions of hemoglobin since 0.4 mM or 2.0 mM of ferric chloride did not
simulate the effects of hemoglobin.
Because neurons can be exposed to hemoglobin in hemorrhagic stroke and head
injuries, the electrophysiological actions of hemoglobin on rat hippocampal CAl neurons
may be relevant to the neurological complications associated with intracranial hemorrhage
and head injuries. Further studies on mechanisms of the electrophysiological actions of
hemoglobin are necessary for understanding the role of hemoglobin in neuronal damages
associated with hemorrhagic stroke and other head injuries.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/5352 |
| Date | 11 1900 |
| Creators | Ip, Joseph Ko Hung |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Relation | UBC Retrospective Theses Digitization Project [http://www.library.ubc.ca/archives/retro_theses/] |
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