Abstract
Using genetically engineered mice and cell lines derived from genetically engineered mice we show that depletion of ER delimited Ca2+ stores activates heteromeric Ca2+ entry (SOCE) channels formed obligatorily, but not exclusively by Orai1 molecules. Comparison of Orai-dependent Ca2+ entries revealed Orai1 to be dominant when compared to Orai2 and Orai3. Unexpectedly, we found that store-depletion- activated Ca2+ entry does not depend obligatorily on functionally intact TRPC molecules, as SOCE monitored with the Fura2 Ca2+ reporter dye is unaffected in cells in which all seven TRPC coding genes have been structurally and functionally inactivated. Unexpectedly as well, we found that TRPC-independent Gq-coupled receptor-operated Ca2+ entry (ROCE) also depends on Orai1. Biophysical measurements of Ca2+ release activated Ca2+ currents (Icrac) are likewise unaffected by ablation of all seven TRPC genes. We refer to mice and cells carrying the seven-fold disruption of TRPC genes as TRPC heptaKO mice and cells. TRPC heptaKO mice are fertile allowing the creation of a new homozygous inbred strain.
Original language | English (US) |
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Article number | e2411389121 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 121 |
Issue number | 49 |
DOIs | |
State | Published - Dec 3 2024 |
Funding
ACKNOWLEDGMENTS. This research was supported by the intramural Research Program of the NIH (Project Z01-ES101684 to L.B.) and NIH Research Grants R01-NS057499 to M.P., R01-AT011162 to R.P., R01CA195727 to L.H., and R35-132349 to M.P. and M.Y.
Keywords
- Orai
- ROCE
- SOCE
- TRPC
ASJC Scopus subject areas
- General