Effects of hemoglobin and its breakdown products on synaptic transmission in rat hippocampal CA1 neurons.
During head injuries and hemorrhagic stroke, blood is released into the extravascular space. The pooled erythrocytes get lysed and hemoglobin is released into the intracranial cavities. Therefore, neurons may be exposed to hemoglobin and/or its breakdown products, hemin and iron, for long periods of time. In this study, the electrophysiological actions of these agents on synaptic transmission in rat hippocampal CA1 pyramidal neurons were studied using extracellular field- and whole cell patch-recordings. Previously our laboratory reported that commercially available hemoglobin produced a dose dependent suppression of synaptic transmission in hippocampal CA1 neurons. In the present study, however, we found that this depression was caused by impurities present in the hemoglobin samples. Commercially available hemoglobin and methemoglobin did not have a significant effect on synaptic transmission. Although, reduced-hemoglobin prepared using a method described by Martin et al. [J. Pharm. Exp. Ther. 232 (1985) 708], produced a significant depression of synaptic transients, these effects were due to contamination with bisulfite that was present due to the reducing procedure. Therefore, the technique of Martin et al. was inadequate in removing the reducing agents or their breakdown products. A number of studies in literature used commercial samples of hemoglobin or reduced hemoglobin prepared using the method of Martin et al. Our observations indicate that it would be important to determine if contaminants, rather than hemoglobin, are responsible for the observed effects in these studies. Unlike hemoglobin, its breakdown products, ferrous chloride and hemin, produced an irreversible and significant depression of field excitatory postsynaptic potentials. The relevance of these effects in neurological complications that follow head injuries and hemorrhagic stroke awaits further investigation.
Yip
S
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Neuroscience Research Laboratory, Department of Pharmacology and Therapeutics, The University of British Columbia, Vancouver, Canada.
Sastry
B R
BR
D000818:Animals; D006259:Craniocerebral Trauma / Q000150:complications* / Q000503:physiopathology; D003956:Dialysis / Q000379:methods; D004340:Drug Contamination; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006427:Hemin / Q000009:adverse effects / Q000378:metabolism; D006454:Hemoglobins / Q000009:adverse effects* / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D020300:Intracranial Hemorrhages / Q000150:complications* / Q000503:physiopathology; D007501:Iron / Q000009:adverse effects / Q000378:metabolism; D008297:Male; D008706:Methemoglobin / Q000009:adverse effects / Q000378:metabolism; D010084:Oxidation-Reduction; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D006454:Hemoglobins; D006427:Hemin; D008706:Methemoglobin; D007501:Iron