A new type of Ca2+ channel blocker that targets Ca2+ sensors and prevents Ca2+-mediated apoptosis

Academic Article

Abstract

  • Calmodulin (CAM), as well as other Ca2+ binding motifs (i.e., EF hands), have been demonstrated to be Ca2+ 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 Ca2+-permeant channels and inhibit biological activity that is dependent on the influx of Ca2+. 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 Ca2+ through these channels was also dose-dependently inhibited by these novel peptides. Thus, this new type of Ca2+ 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
  • Digital Object Identifier (doi)

    Author List

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

  • 1297
  • End Page

  • 1306
  • Volume

  • 14
  • Issue

  • 10