A new type of Ca(2+) channel blocker that targets Ca(2+) sensors and prevents Ca(2+)-mediated apoptosis.

Academic Article

Abstract

  • 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.
  • Authors

    Published In

  • The FASEB Journal  Journal
  • Keywords

  • Amino Acid Sequence, Animals, Apoptosis, Biological Transport, Active, Calcium, Calcium Channel Blockers, Calcium Signaling, Cells, Cultured, Drug Design, Humans, Jurkat Cells, Neurons, Oligopeptides, Rats, Receptors, Glutamate
  • Digital Object Identifier (doi)

    Pubmed Id

  • 22559114
  • Author List

  • Manion MK; Su Z; Villain M; Blalock JE
  • Start Page

  • 1297
  • End Page

  • 1306
  • Volume

  • 14
  • Issue

  • 10