Involvement of a Gardos-type potassium channel in head activator-induced mitosis of BON cells

Eur J Cell Biol. 1998 Jun;76(2):119-24. doi: 10.1016/s0171-9335(98)80024-1.


The human neuroendocrine cell line BON was used to study second messengers involved in signal transduction for entry into mitosis. BON cells produce the neuropeptide head activator (HA) and use it as autocrine growth factor. HA stimulates BON cell proliferation by triggering entry into mitosis. HA-induced mitosis is mediated by an inhibitory G protein, the action of which is blocked by pertussis toxin. HA signaling requires inhibition of the cAMP pathway, calcium influx, and hyperpolarization of cells. The latter is a very important and sensitive step involving a calcium-activated potassium channel. Cell cycle progression and proliferation of BON cells are most efficiently inhibited with specific inhibitors of this potassium channel. Pharmacology and RNA analysis suggest identity with the recently cloned Gardos-type potassium channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autocrine Communication
  • Blotting, Northern
  • Calcium / metabolism*
  • Cell Count / drug effects
  • Cell Cycle
  • Clotrimazole / pharmacology
  • Cyclic AMP / metabolism
  • Flow Cytometry
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Growth Substances / physiology
  • Humans
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Mitosis / drug effects*
  • Neuropeptides / agonists
  • Neuropeptides / metabolism
  • Neuropeptides / pharmacology*
  • Pancreas / cytology
  • Potassium / metabolism
  • Potassium Channel Blockers
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Potassium Channels, Calcium-Activated*
  • Pyrrolidonecarboxylic Acid / analogs & derivatives
  • Radioimmunoassay
  • Second Messenger Systems / drug effects
  • Signal Transduction
  • Tumor Cells, Cultured


  • Growth Substances
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • KCNN4 protein, human
  • Neuropeptides
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • head activator peptide
  • Cyclic AMP
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Clotrimazole
  • Potassium
  • Calcium
  • Pyrrolidonecarboxylic Acid