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A new type of Ca 2+ channel blocker that targets Ca 2+ sensors and prevents Ca 2+ ‐mediated apoptosis
Author(s) -
Manion Michael K.,
Su Zhengchang,
Villain Matteo,
Blalock J. Edwin
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.14.10.1297
Subject(s) - channel blocker , jurkat cells , apoptosis , calmodulin , chemistry , ion channel , ligand gated ion channel , biophysics , receptor , microbiology and biotechnology , calcium , biochemistry , biology , immunology , t cell , immune system , organic chemistry
Calmodulin (CaM), as well as other Ca 2+ binding motifs (i.e., EF hands), have been demonstrated to be Ca 2+ sensors for several ion channel types, usually resulting in an inactivation in a negative feedback manner. This provides a novel target for the regulation of such channels. We have designed peptides that interact with EF hands of CaM in a specific and productive manner. Here we have examined whether these peptides block certain Ca 2+ ‐permeant channels and inhibit biological activity that is dependent on the influx of Ca 2+ . We found that these peptides are able to enter the cell and directly, as well as indirectly (through CaM), block the activity of glutamate receptor channels in cultured neocortical neurons and a nonselective cation channel in Jurkat T cells that is activated by HIV‐1 gp120. As a consequence, apoptosis mediated by an influx of Ca 2+ through these channels was also dose‐dependently inhibited by these novel peptides. Thus, this new type of Ca 2+ channel blocker may have utility in controlling apoptosis due to HIV infection or neuronal loss due to ischemia.—Manion, M. K., Su, Z., Villain, M., Blalock, J. E. A new type of Ca 2+ channel blocker that targets Ca 2+ sensors and prevents Ca 2+ ‐mediated apoptosis. FASEB J. 14, 1297–1306 (2000)