Related Experiment Video
Updated: Aug 24, 2026

Fluorescence-based Measurement of Store-operated Calcium Entry in Live Cells: from Cultured Cancer Cell to Skeletal Muscle Fiber
Published on: February 13, 2012
Two types of store-operated Ca2+ channels with different activation modes and molecular origin in LNCaP human
Fabien Vanden Abeele1, Loic Lemonnier, Stéphanie Thébault
1Laboratoire de Physiologie Cellulaire, INSERM EMI-0228, Université des Sciences et Technologies de Lille, Bat. SN3, 59655 Villeneuve d'Ascq, France.
Abstract:
The one or more coupling mechanisms of store-operated channels (SOCs) to endoplasmic reticulum (ER) Ca2+ store depletion as well as the molecular identity of SOCs per se still remain a mystery. Here, we demonstrate the co-existence of two populations of molecular distinct endogenous SOCs in LNCaP prostate cancer epithelial cells, which are preferentially activated by either active inositol 1,4,5-trisphosphate (IP3)-mediated or passive thapsigargin-facilitated store depletion and have different ER store content sensitivity. The first population, called SOC(CC) (for "conformational coupling"), is characterized by preferential IP3 receptor-dependent mode of activation, as judged from sensitivity to cytoskeleton modifications, and dominant contribution of transient receptor potential (TRP) TRPC1 within it. The second one, called SOC(CIF) (for "calcium influx factor"), depends on Ca(2+)-independent phospholipase A2 for activation with probable CIF involvement and is mostly represented by TRPC4. The previously identified SOC constituent in LNCaP cells, TRPV6, seems to play equal role in both SOC populations. These results provide new insight into the nature of SOCs and their representation in the single cell type as well as permit reconciliation of current SOC activation hypotheses.
Insights
Two distinct types of store-operated calcium channels (SOCs) were identified in prostate cancer cells. These channels differ in their activation mechanisms and store depletion sensitivity, offering new insights into calcium signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Calcium Signaling
Background:
- The precise mechanisms coupling store-operated channels (SOCs) to endoplasmic reticulum (ER) calcium (Ca2+) store depletion remain unclear.
- The molecular identity of SOCs themselves is not fully elucidated.
Purpose of the Study:
- To investigate the molecular identity and activation mechanisms of SOCs in LNCaP prostate cancer cells.
- To differentiate between distinct SOC populations and their relationship to ER Ca2+ store depletion.
Main Methods:
- Utilized LNCaP prostate cancer epithelial cells.
- Investigated SOC activation via inositol 1,4,5-trisphosphate (IP3)-mediated and thapsigargin-facilitated ER store depletion.
- Analyzed the contribution of TRPC1, TRPC4, and TRPV6 to SOC function.
Main Results:
- Demonstrated the co-existence of two molecularly distinct endogenous SOC populations in LNCaP cells.
- Identified SOC(CC) (conformational coupling) activated by IP3 receptors and TRPC1, and SOC(CIF) (calcium influx factor) activated by Ca2+-independent phospholipase A2 and TRPC4.
- TRPV6 was found to play a role in both SOC populations.
Conclusions:
- These findings reveal novel insights into the heterogeneity of SOCs within a single cell type.
- The results reconcile current hypotheses regarding SOC activation mechanisms and provide a clearer understanding of their molecular basis.
Related Concept Videos
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated Ion Channels
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Ion Channels
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Amplifying Signals via Second Messengers
Mechanically-gated Ion Channels

