Transient in vivo membrane depolarization and glutamate release before anoxic depolarization in rat striatum.
Increased extracellular glutamate ([GLU]e), under the condition of cerebral ischemia, anoxia or hypoxia, has been recognized as being associated with neuronal cell damage and death. We performed real-time monitoring of [GLU]e dynamics in vivo in the rat striatum during systemic acute anoxia or hypoxia, as well as monitoring the direct current potential (DC) and cerebral blood flow (CBF). Adult Wistar rats were orotracheally intubated and artificially ventilated with room air. A microdialysis electrode, temperature sensor probe, DC microelectrode and laser Doppler probe were then implanted. The inspired gas was changed to 100% N(2) (anoxia), or to 3, 5 or 8% O(2) (remainder N(2)) (hypoxia). With 100% N(2), distinct biphasic [GLU]e elevations were observed. With 3% O(2), a transient [GLU]e increase was seen before anoxic depolarization (AD). With 5% O(2), however, the start of the transient [GLU]e increase was significantly delayed. Anoxia-induced depolarization started at about 100 s. The 3% O(2)-induced transient depolarization and AD began at nearly the same time as the transient and AD-induced increase in [GLU]e. Similarly, the responses to 5% O(2) showed significant delays in the transient depolarization and AD-induced increase in [GLU]e. CBF during 3 or 5% O(2) hypoxic insult was consistently maintained above the control level, i.e., prior to cardiac arrest. Our new dialysis electrode method employing both GOX and ferrocene-conjugated bovine serum albumin allowed evaluation of transient [GLU]e dynamics in the early phase of severe hypoxia in vivo.
Department of Pharmacology, Nihon University School of Medicine, Oyaguchi-Kami Machi, Itabashi-ku, Tokyo 173, Japan.
T
T
Kunimatsu
S
S
Asai
K
K
Kanematsu
H
H
Zhao
T
T
Kohno
T
T
Misaki
K
K
Ishikawa
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003199:Computer Systems; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017551:Microdialysis; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010455:Peptides; D018698:Glutamic Acid; D020866:omega-Conotoxin GVIA