Protection of TRPC7 cation channels from calcium inhibition by closely associated SERCA pumps

Numerous studies have demonstrated that members of the transient receptor potential (TRP) superfamily of channels are involved in regulated Ca2+ entry. Additionally, most Ca2+‐permeable channels are themselves regulated by Ca2+, often in complex ways. In the current study, we have investigated the r...

Full description

Saved in:
Bibliographic Details
Published in:The FASEB journal 2006-03, Vol.20 (3), p.503-505
Main Authors: Lemonnier, Loïc, Trebak, Mohamed, Lievremont, Jean-Philippe, Bird, Gary S, Putney, James W
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Boron Compounds - pharmacology
Calcium - pharmacology
calcium channels
calcium signaling
Calcium-Transporting ATPases - antagonists & inhibitors
Calcium-Transporting ATPases - physiology
Calmodulin - physiology
Cations - metabolism
Cytochalasin B - pharmacology
Cytoskeleton - drug effects
Cytoskeleton - physiology
Depsipeptides - pharmacology
Diglycerides - pharmacology
Drosophila melanogaster
Gadolinium - pharmacology
Humans
Imidazoles - pharmacology
Indoles - pharmacology
ion channels
Ion Transport
Life Sciences
Thapsigargin - pharmacology
TRPC Cation Channels - antagonists & inhibitors
TRPC Cation Channels - metabolism
TRPC channels
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Numerous studies have demonstrated that members of the transient receptor potential (TRP) superfamily of channels are involved in regulated Ca2+ entry. Additionally, most Ca2+‐permeable channels are themselves regulated by Ca2+, often in complex ways. In the current study, we have investigated the regulation of TRPC7, a channel known to be potentially activated by both store‐operated mechanisms and non‐store‐operated mechanisms involving diacylglycerols. Surprisingly, we found that activation of TRPC7 channels by diacylglycerol was blocked by the SERCA pump inhibitor thapsigargin. The structurally related channel, TRPC3, was similarly inhibited. This effect depended on extracellular calcium and on the driving force for Ca2+ entry. The inhibition is not due to calcium entry through store‐operated channels but rather results from calcium entry through TRPC7 channels themselves. The effect of thapsigargin was prevented by inhibition of calmodulin and was mimicked by pharmacological disruption of the actin cytoskeleton. Our results suggest the presence of a novel mechanism involving negative regulation of TRPC channels by calcium entering through the channels. Under physiological conditions, this negative feedback by calcium is attenuated by the presence of closely associated SERCA pumps.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.05-4714fje