Referenced in: none

Automatically associated channels: Cav3.2

Title: The role of voltage gated T-type Ca2+ channel isoforms in mediating "capacitative" Ca2+ entry in cancer cells.

Authors: Lloyd S Gray, Edward Perez-Reyes, Juan Carlos Gomora, Juan Carlos Gamorra, Doris M Haverstick, Michael Shattock, Linda McLatchie, Jane Harper, Gavin Brooks, Tiffany Heady, Timothy L Macdonald

Journal, date & volume: Cell Calcium, 2004 Dec , 36, 489-97

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15488598

Abstract
The mechanism by which Ca2+ enters electrically non-excitable cells is unclear. The sensitivity of the Ca2+ entry pathway in electrically non-excitable cells to inhibition by extracellular Ni2+ was used to direct the synthesis of a library of simple, novel compounds. These novel compounds inhibit Ca2+ entry into and, consequently, proliferation of several cancer cell lines. They showed stereoselective inhibition of proliferation and Ca2+ influx with identical stereoselective inhibition of heterologously expressed Cav3.2 isoform of T-type Ca2+ channels. Proliferation of human embryonic kidney (HEK)293 cells transfected with the Cav3.2 Ca2+ channel was also blocked. Cancer cell lines sensitive to our compounds express message for the Cav3.2 T-type Ca2+ channel isoform, its delta25B splice variant, or both, while a cell line resistant to our compounds does not. These observations raise the possibility that clinically useful drugs can be designed based upon the ability to block these Ca2+ channels.