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Updated: Jul 10, 2026

Cytosolic Calcium Measurements in Renal Epithelial Cells by Flow Cytometry
Published on: October 28, 2014
Cation channels in human embryonic kidney cells mediating calcium entry in response to extracellular low glucose
1Department of Physiology, The Medical School, University of Birmingham, Edgbaston B15 2TT, UK.
Abstract:
Glucose sensing mechanism has been intensively studied in pancreatic cells and neurons. Depolarization of membrane potential by closure of K(ATP) , Kv and TASK channel, and subsequently Ca(2+) entry via L-type voltage gated Ca(2+) channel (VGCC) are implicated to mediate the signal transduction in these cells. However, the mechanism of non-excitable cells, which are lacking VGCC, for sensing glucose remains unclear. In this study, we utilized the calcium ratio measurement and patch clamping technique to study the effects of low glucose on [Ca(2+)](i) and currents in the human embryonic kidney epithelial cells (HEK 293). We found low glucose evoked a significant reversible [Ca(2+)](i) elevation in HEK 293 independent of the closure of Kv channels. This increase of [Ca(2+)](i) was mediated by Ca(2+) entry across plasma membrane and exhibited a dosage dependent behaviour to external glucose concentration. The low glucose-induced entry of Ca(2+) was characterized as a voltage independent behaviour and had cation permeability to Na(+) and Ca(2+). The modulation of PLC, AMPK, tyrosine kinase and cADPribose failed to regulate this glucose-sensitive Ca(2+) entry. In addition, the entry of Ca(2+) was insensitive to nifedipine, 2APB, SKF, La(3+), Gd(3+), and KBR9743, suggesting a novel signal pathway in mediating glucose sensing.
Insights
Low glucose triggers calcium (Ca2+) elevation in non-excitable HEK 293 cells, independent of known channels. This suggests a novel glucose sensing pathway in cells lacking voltage-gated calcium channels (VGCC).
Area of Science:
- Cellular Biology
- Physiology
- Biochemistry
Background:
- Glucose sensing is well-studied in excitable cells like pancreatic cells and neurons.
- These cells utilize K(ATP), Kv, and TASK channels, and voltage-gated calcium channels (VGCC) for glucose-induced signaling.
- The glucose sensing mechanism in non-excitable cells, which lack VGCC, remains largely unknown.
Purpose of the Study:
- To investigate the mechanism of glucose sensing in non-excitable human embryonic kidney epithelial cells (HEK 293).
- To determine the role of calcium ion (Ca2+) influx in response to low glucose in these cells.
Main Methods:
- Utilized calcium ratio measurement to monitor intracellular Ca2+ levels ([Ca2+]i).
- Employed patch clamping techniques to study ion currents.
- Tested the effects of various modulators and inhibitors on glucose-induced Ca2+ entry.
Main Results:
- Low glucose induced a significant, reversible increase in [Ca2+]i in HEK 293 cells.
- This Ca2+ elevation was mediated by Ca2+ entry across the plasma membrane, independent of Kv channel closure.
- The Ca2+ entry was voltage-independent, permeable to Na+ and Ca2+, and unaffected by common signaling pathway modulators or channel blockers.
Conclusions:
- HEK 293 cells possess a novel glucose-sensing mechanism involving voltage-independent Ca2+ entry.
- This pathway does not rely on previously identified glucose-sensing components like VGCC or modulation by PLC, AMPK, or tyrosine kinase.
- Further research is needed to elucidate the specific molecular players in this newly identified glucose-sensitive pathway.
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