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Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+
Published on: May 19, 2017
A light-addressable potentiometric sensor-based extracellular calcium dynamic monitoring and imaging platform for
Shichao Tian1, Chiyu Ma2, Yuxuan Zhu1
1Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027, China.
Abstract:
Disruption and dysregulation of cellular calcium channel function can lead to diseases such as ischemic stroke, heart failure, and arrhythmias. Corresponding calcium channel drugs typically require preliminary efficacy evaluations using in vitro models such as cells and simulated tissues before clinical testing. However, traditional detection and evaluation methods often encounter challenges in long-term continuous monitoring and lack calcium specificity. In this study, a dynamic monitoring system based on ion-sensitive membranes for light-addressable potentiometric sensor (LAPS) was developed to meet the demand for monitoring changes in extracellular calcium ion (Ca2+) concentration in live cells. The effects of Ca2+ channel agonists and blockers on 2D and 3D HL-1 cells were investigated, with changes in extracellular Ca2+ concentration reflecting cellular calcium metabolism, facilitating drug evaluation. Additionally, calcium imaging technology with optical addressing capability complemented the LAPS system's ability to perceive 3D cell morphology, enhancing its drug evaluation capabilities. This work provides a novel, label-free, specific, and stable technique for monitoring cellular calcium metabolism. It achieves both continuous monitoring at single points and custom sensing area calcium imaging, holding significant implications for drug screening and disease treatment related to human calcium homeostasis.
Insights
A new light-addressable potentiometric sensor (LAPS) system enables continuous, specific monitoring of cellular calcium. This dynamic system aids in evaluating calcium channel drugs for diseases like stroke and heart failure.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Sensor Technology
Background:
- Cellular calcium channel dysfunction is linked to severe diseases, including stroke, heart failure, and arrhythmias.
- Current in vitro drug evaluation methods for calcium channel modulators face limitations in long-term monitoring and calcium specificity.
- There is a need for advanced techniques to accurately assess cellular calcium metabolism in real-time.
Purpose of the Study:
- To develop a novel dynamic monitoring system for real-time extracellular calcium ion (Ca2+) concentration in live cells.
- To evaluate the efficacy of calcium channel agonists and blockers using the developed system.
- To enhance drug screening capabilities for calcium homeostasis-related diseases.
Main Methods:
- Development of a light-addressable potentiometric sensor (LAPS) system incorporating ion-sensitive membranes.
- Application of the LAPS system for monitoring extracellular Ca2+ concentration changes in 2D and 3D HL-1 cell cultures.
- Integration of calcium imaging technology with optical addressing for 3D cell morphology perception.
Main Results:
- The LAPS system successfully monitored dynamic changes in extracellular Ca2+ concentration, reflecting cellular calcium metabolism.
- The system demonstrated the effects of Ca2+ channel agonists and blockers on HL-1 cells.
- Combined LAPS and calcium imaging provided enhanced capabilities for evaluating drug effects on cellular calcium.
Conclusions:
- A novel, label-free, specific, and stable technique for monitoring cellular calcium metabolism has been established.
- The system supports both continuous single-point monitoring and custom sensing area calcium imaging.
- This technology has significant implications for drug screening and the treatment of diseases involving calcium homeostasis disruption.
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