| 12543454 |
Takano H, Fukushi H, Morishima Y, Shirasaki Y: Calmodulin and calmodulin-dependent kinase II mediate neuronal cell death induced by depolarization. Brain Res. 2003 Feb 7;962(1-2):41-7.
Depolarization has been known to play an important role in the neuronal damage that occurs following cerebral ischemia. In the present study, we investigated the roles of calmodulin (CaM) and CaM-dependent enzymes in depolarization-induced neuronal cell death. Treatment of primary cortical neurons with 10 microM veratridine, a voltage sensitive Na (+) channel activator, induced cell death as indicated by lactate dehydrogenase leakage from neurons. CaM antagonists (calmidazolium, trifluoperazine, W-7, and W-5) inhibited cell death induced by veratridine in a concentration-dependent manner. CaM kinase II (CaMKII) inhibitors (KN-62, KN-93, and myristoylated autocamtide-2 related inhibitory peptide), but not inhibitors of nitric oxide synthase or calcineurin, prevented veratridine-induced neuronal cell death. Veratridine rapidly activated CaMKII in neurons, and CaM antagonists and a CaMKII inhibitor suppressed the CaMKII activation. These results suggest that the CaM-CaMKII pathway contributes to depolarization-evoked cell death in neurons. |
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