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Ionic events induced by epidermal growth factor. Evidence that hyperpolarization and stimulated cation influx play a

M Magni1, J Meldolesi, A Pandiella

  • 1Department of Pharmacology, Scientific Institute S. Raffaele, University of Milano, Italy.

The Journal of Biological Chemistry
|April 5, 1991
PubMed

Insights

Epidermal growth factor (EGF) triggers cell growth by influencing ion channel activity. Blocking calcium (Ca2+) channels with SC38249 significantly inhibits EGF-stimulated growth, highlighting the role of Ca2+ influx in mitogenesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • Epidermal growth factor (EGF) receptor signaling is crucial for cell proliferation.
  • Ionic events, including changes in intracellular calcium ([Ca2+]i) and membrane potential, are known to be activated by EGF.
  • The precise role of these ionic events in EGF-mediated cell growth requires further elucidation.

Purpose of the Study:

  • To characterize the ionic events induced by EGF in NIH-3T3 fibroblasts overexpressing the EGF receptor.
  • To determine the role of specific ion channels (K+ and Ca2+) in EGF-activated ionic responses.
  • To establish the contribution of these ionic events to EGF-stimulated cell growth and mitogenesis.

Main Methods:

  • Utilized charybdotoxin (K+ channel blocker) and SC38249 (Ca2+ channel blocker) in mouse NIH-3T3 fibroblasts.
  • Measured intracellular calcium ([Ca2+]i) and membrane potential changes in response to EGF.
  • Assessed cell viability and growth following treatment with ion channel blockers and EGF stimulation.

Main Results:

  • Charybdotoxin partially inhibited EGF-induced hyperpolarization but did not significantly alter the [Ca2+]i response.
  • SC38249 blocked the sustained phase of EGF-induced [Ca2+]i increase and hyperpolarization, which are dependent on Ca2+ influx.
  • While ion channel blockers did not affect unstimulated cell growth, SC38249 markedly inhibited EGF-stimulated growth (-60%), and charybdotoxin caused moderate inhibition (-20%).

Conclusions:

  • EGF-induced hyperpolarization and, particularly, the persistent increase in [Ca2+]i sustained by Ca2+ influx are critical for EGF's mitogenic activity.
  • These ionic events cooperate with other intracellular pathways to drive cell proliferation.
  • Targeting Ca2+ influx pathways represents a potential strategy for modulating EGF-driven cell growth.

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