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Updated: May 27, 2026

Voltage and Calcium Dual Channel Optical Mapping of Cultured HL-1 Atrial Myocyte Monolayer
Published on: March 23, 2015
Store-operated calcium entry is present in HL-1 cardiomyocytes and contributes to resting calcium
Chad D Touchberry1, Chris J Elmore, Tien M Nguyen
1School of Medicine, Muscle Biology Research Group, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
Insights
HL-1 cells, a unique cardiac cell line, effectively model store-operated calcium entry (SOCE). This model aids research into SOCE
Area of Science:
- Cardiology
- Cell Biology
- Calcium Signaling
Background:
- Store-operated Ca(2+) entry (SOCE) is crucial in cardiac function and disease, but difficult to study in primary cardiomyocytes.
- HL-1 cells offer a stable, immortalized in vitro model for cardiomyocyte research.
Purpose of the Study:
- To investigate the role and mechanisms of SOCE in HL-1 cardiac cells.
- To establish HL-1 cells as a reliable model for studying SOCE in the heart.
Main Methods:
- Assessed expression of SOCE components (STIM1, Orai1) in HL-1 cells.
- Measured intracellular Ca(2+) changes during SOCE using inhibitors and Orai1 knockdown (RNAi).
- Examined SOCE coupling with sarcoplasmic reticulum Ca(2+) release and other ion channels.
Main Results:
- HL-1 cells express STIM1 and Orai1, key for SOCE.
- SOCE in HL-1 cells is linked to sarcoplasmic reticulum Ca(2+) release and unaffected by other channel inhibitors.
- Orai1 knockdown reduced baseline Ca(2+) and attenuated responses to thapsigargin and caffeine.
Conclusions:
- HL-1 cells are a valuable in vitro model for studying SOCE in cardiomyocytes.
- SOCE may influence Ca(2+) homeostasis in unstressed cardiomyocytes.
- This model can advance research on SOCE's role in cardiac pathology and drug development.
Abstract:
Store-operated Ca(2+) entry (SOCE) has recently been shown to be of physiological and pathological importance in the heart, particularly during cardiac hypertrophy. However, measuring changes in intracellular Ca(2+) during SOCE is very difficult to study in adult primary cardiomyocytes. As a result there is a need for a stable and reliable in vitro model of SOCE which can be used to test cardiac drugs and investigate the role of SOCE in cardiac pathology. HL-1 cells are the only immortal cardiomyocyte cell line available that continuously divides and spontaneously contracts while maintaining phenotypic characteristics of the adult cardiomyocyte. To date the role of SOCE has not yet been investigated in the HL-1 cardiac cell line. We report for the first time that these cells expressed stromal interaction molecule 1 (STIM1) and the Ca(2+) release-activated Ca(2+) (CRAC) channel Orai1, which are essential components of the SOCE machinery. In addition, SOCE was tightly coupled to sarcoplasmic reticulum (SR)-Ca(2+) release in HL-1 cells, and such response was not impaired in the presence of voltage dependent Ca(2+) channels (L-type and T-type channels) or reverse mode Na(+)/Ca(2+) exchanger (NCX) inhibitors. We were able to abolish the SOCE response with known SOCE inhibitors (BTP-2 and SKF-96365) and by targeted knockdown of Orai1 with RNAi. In addition, knockdown of Orai1 resulted in lower baseline Ca(2+) and an attenuated response to thapsigargin (TG) and caffeine, indicating that SOCE may play a role in Ca(2+) homeostasis during unstressed conditions in cardiomyocytes. Currently, there is little knowledge about SOCE in cardiomyocytes, and the present results suggest that HL-1 cells will be of great utility in investigating the role of SOCE in the heart.
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