A role for voltage gated T-type calcium channels in mediating "capacitative" calcium entry?
Calcium entry through plasma membrane calcium channels is one of the most important cell signaling mechanism involved in such diverse functions as secretion, contraction and cell growth by regulating gene expression, proliferation and apoptosis. The identity of plasma membrane calcium channels, the main regulators of calcium entry, involved in cell proliferation has been thus extensively sought. Among these, a calcium entry pathway called capacitative calcium entry (CCE), activated by calcium store depletion, is particularly important in non-excitable cells. Though this capacitative calcium entry is generally supposed to occur through TRP channels there is some evidence that voltage-dependent T-type calcium channels may contribute to calcium entry after store depletion. Here we show that though mibefradil, a T-type calcium channel blocker, is able to reduce capacitative calcium entry induced by either thapsigargin or ATP, this was not mimicked by any other T-type calcium channel inhibitors even in cells overexpressing alpha(1H) T-type calcium channels, leading us to conclude that T-type calcium channels are not responsible for the capacitative calcium entry observed in different cancer cell lines. On the contrary, we show that the action of mibefradil on capacitative calcium entry is due to an action on store-operated calcium channels.
Gackière
Florian
F
Laboratoire de Physiologie Cellulaire, INSERM EMI0228, Bâtiment SN3, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France.
Bidaux
Gabriel
G
Lory
Philippe
P
Prevarskaya
Natalia
N
Mariot
Pascal
P
D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D017136:Ion Transport / Q000502:physiology; D020748:Mibefradil / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020747:Calcium Channels, T-Type; D012333:RNA, Messenger; D020748:Mibefradil; D002118:Calcium