Premium
The Potassium Channel Opener (−)‐Cromakalim Prevents Glutamate‐Induced Cell Death in Hippocampal Neurons
Author(s) -
Lauritzen Inger,
De Weille Jan R.,
Lazdunski Michel
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69041570.x
Subject(s) - cromakalim , glutamate receptor , potassium channel opener , potassium channel , chemistry , glibenclamide , pharmacology , medicine , biology , endocrinology , biochemistry , receptor , diabetes mellitus
(−)‐Cromakalim, a typical K + ‐channel opener, prevents neuronal death induced by either glucose and oxygen privation or by high (100 µ M ) extracellular glutamate in primary cultures of hippocampus. (−)‐Cromakalim has no effect on the earliest events associated with exposure to glutamate. It does not prevent the rapid rise of intracellular Ca 2+ , the initial swelling of neurons, or the induction of c‐ fos mRNA transcription. (−)‐Cromakalim inhibits all delayed effects associated with the excitotoxic effect of glutamate: (a) (−)‐cromakalim inhibits the late and major phase of intracellular Ca 2+ increase occurring up to hours after glutamate application; and (b) although (−)‐cromakalim cannot prevent the initial cellular swelling induced by glutamate, cells that have been pretreated with (−)‐cromakalim return to their original size in a few hours, whereas non‐(−)‐cromakalim‐treated cells remain swollen for more prolonged periods. Many neurons surviving the initial necrotic phase of glutamate‐induced cell death undergo progressive DNA cleavage leading to apoptosis. This apoptotic process is prevented completely by (−)‐cromakalim. Glibenclamide, a potent blocker of the ATP‐sensitive K + channel, abolishes all the beneficial effects of (−)‐cromakalim. These findings strongly suggest that (−)‐cromakalim has postsynaptic effects that are closely related to the regulation of Ca 2+ homeostasis and cell volume.