Cation channels in human embryonic kidney cells mediating calcium entry in response to extracellular low glucose.
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.
Wang
Su
S
Department of Physiology, The Medical School, University of Birmingham, Edgbaston B15 2TT, UK.
Gu
Yuchun
Y
D002118:Calcium / Q000493:pharmacokinetics*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D050051:Transient Receptor Potential Channels; D005947:Glucose; D002118:Calcium