5-HT3 receptors induce rises in cytosolic and nuclear calcium in NG108-15 cells via calcium-induced calcium release

Cell Calcium. 1997 Nov;22(5):357-65. doi: 10.1016/s0143-4160(97)90020-8.


A complete understanding of how excitatory ligand-gated ion channels regulate intracellular Ca2+ in nerve cells remains to be elucidated. Laser-scanning confocal microscopy was used here to measure Ca2+ changes in the neuroblastoma x glioma hybrid cell line NG108-15, employed as a model nerve cell line, upon activation by the 5-HT3 receptor, a serotonin-activated ligand-gated ion channel. Addition of the 5-HT3 agonist 1-m-(chlorophenyl)-biguanide (mCPBG) induced increases in [Ca2+]i in both the cytoplasm and the nuclei of the NG108-15 cells. Using high-time resolution line scanning, no delay was evident between the mCPBG-induced rise in cytosolic [Ca2+]i and the rise in nuclear [Ca2+]i. The agonist-induced responses were completely blocked by addition of EGTA to chelate external Ca2+ and by addition of the 5-HT3 receptor antagonist tropisetron or the L-type Ca2+ channel blocker nitrendipine. Caffeine, but not thapsigargin, treatment significantly reduced the mCPBG-induced responses in the nucleus and the cytoplasm, both to the same extent. We conclude that, upon 5-HT3 receptor activation, Ca2+ enters the cells through voltage-gated Ca2+ channels and then triggers the release of Ca2+ from ryanodine-sensitive intracellular stores, greatly amplifying the increases in Ca2+ in the cytoplasm and the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biguanides / metabolism
  • Biguanides / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • Hybrid Cells
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT3
  • Serotonin Receptor Agonists / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Tumor Cells, Cultured


  • Biguanides
  • Calcium Channels
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Receptor Agonists
  • 1-(3-chlorophenyl)biguanide
  • Calcium