Cation channels in human embryonic kidney cells mediating calcium entry in response to extracellular low glucose

Su Wang1, Yuchun Gu

  • 1Department of Physiology, The Medical School, University of Birmingham, Edgbaston B15 2TT, UK.

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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