Ion channel involvement in anoxic depolarization induced by cardiac arrest in rat brain.
Anoxic depolarization (AD) and failure of ion homeostasis play an important role in ischemia-induced neuronal injury. In the present study, different drugs with known ion-channel-modulating properties were examined for their ability to interfere with cardiac-arrest-elicited AD and with the changes in the extracellular ion activity in rat brain. Our results indicate that only drugs primarily blocking membrane Na+ permeability (NBQX, R56865, and flunarizine) delayed the occurrence of AD, while compounds affecting cellular Ca2+ load (MK-801 and nimodipine) did not influence the latency time. The ischemia-induced [Na+]e reduction was attenuated by R56865. Blockade of the ATP-sensitive K+ channels with glibenclamide reduced the [K+]e increase upon ischemia, indicating an involvement of the KATP channels in ischemia-induced K+ efflux. The KATP channel opener cromakalim did not affect the AD or the [K+]e concentration. The ischemia-induced rapid decline of extracellular calcium was attenuated by receptor-operated Ca2+ channel blockers MK-801 and NBQX, but not by the voltage-operated Ca2+ channel blocker nimodipine, R56865, and flunarizine.
Xie
Y
Y
Preclinical Research, Janssen GmbH, Neuss, Germany.
Zacharias
E
E
Hoff
P
P
Tegtmeier
F
F
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006323:Heart Arrest / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology
D052160:Benzothiazoles; D007473:Ion Channels; D010880:Piperidines; D015221:Potassium Channels; D011810:Quinoxalines; D013844:Thiazoles; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D009553:Nimodipine; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; C054551:R 56865; D012964:Sodium; D005444:Flunarizine; D011188:Potassium; D005905:Glyburide; D002118:Calcium