Participation of the Ca2+-calmodulin-activated kinase II in the control of metaphase-anaphase transition in human cells

Treatment of HeLa S3 cells growing in suspension, and of endothelial cells ECV 304 growing as a monolayer, with the inhibitor of the Ca2+-calmodulin activated Kinase II KN-93, blocks cells at metaphase for 15 min (HeLa cells) and 30 min (ECV cells). Thereafter cells resume mitosis and enter anaphase. The inactive isomer KN-92 does not show such effects. The results show the involvement of the CaM K II system in the regulation of the metaphase-anaphase transition whereby the activation of the Kinase II, in particular by calmodulin appears to be affected, the residual autophosphorylation of the CaM K II system apparently sufficing after 15 to 30 min to release the cells into anaphase. The results are compared with the metaphase-blocking effects of the noble gas xenon, where the xenon-induced block can be overcome by small intracellular increases of Ca2+, thus indicating the CaM K II system as a possible target for xenon. (C) 2001 Academic Press.