Effects of 50 Hz electromagnetic fields on voltage-gated Ca2+ channels and their role in modulation of neuroendocrine cell proliferation and death

• Published in: Cell calcium (Edinburgh) 2004-04, Vol.35 (4), p.307
• Main Authors: Grassi, Claudio, D'Ascenzo, Marcello, Torsello, Angela, Martinotti, Giovanni, Wolf, Federica, Cittadini, Achille, Azzena, Gian Battista
• Format: Article
• Language: English
• Subjects: Animals; Antimetabolites, Antineoplastic - pharmacology; Apoptosis - drug effects; Apoptosis - radiation effects; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - radiation effects; Calcium Channels, N-Type - radiation effects; Cell Division - drug effects; Cell Division - radiation effects; Cell Membrane - chemistry; Cell Membrane - metabolism; Cells, Cultured; Electromagnetic Fields; Electrophysiology; Humans; Hydrogen Peroxide - pharmacology; Neuroblastoma - metabolism; Neuroblastoma - pathology; Oxidants - pharmacology; Patch-Clamp Techniques; Pituitary Gland - cytology; Pituitary Gland - metabolism; Puromycin - pharmacology; Rats
• ISSN: 0143-4160
• DOI: 10.1016/j.ceca.2003.09.001

Possible correlation between the effects of electromagnetic fields (EFs) on voltage-gated Ca(2+) channels, cell proliferation and apoptosis was investigated in neural and neuroendocrine cells. Exposure to 50 Hz EFs significantly enhanced proliferation in human neuroblastoma IMR32 (+40%) and rat pituitary GH3 cells (+38%). In IMR32 cells EF stimulation also inhibited puromycin- and H(2)O(2)-induced apoptosis (-22 and -33%, respectively). EF effects on proliferation and apoptosis were counteracted by Ca(2+) channel blockade. In whole-cell patch-clamp experiments 24-72 h exposure to EFs increased macroscopic Ba(2+)-current density in both GH3 (+67%) and IMR32 cells (+40%). Single-channel recordings showed that gating of L and N channels was instead unaffected, thus suggesting that the observed enhancement of current density was due to increased number of voltage-gated Ca(2+) channels. Western blot analysis of plasma membrane-enriched microsomal fractions of GH3 and IMR32 cells confirmed enhanced expression of Ca(2+) channel subunit alpha(1) following exposure to EFs. These data provide the first direct evidence that EFs enhance the expression of voltage-gated Ca(2+) channels on plasma membrane of the exposed cells. The consequent increase in Ca(2+) influx is likely responsible for the EF-induced modulation of neuronal cell proliferation and apoptosis.