Effects of 50 Hz electromagnetic fields on voltage-gated Ca2+ channels and their role in modulation of neuroendocrine cell proliferation and death.
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.
Grassi
Claudio
C
Institute of Human Physiology, Medical School, Catholic University S. Cuore, Largo F. Vito 1, 00168 Rome, Italy. grassi@rm.unicatt.it
D'Ascenzo
Marcello
M
Torsello
Angela
A
Martinotti
Giovanni
G
Wolf
Federica
F
Cittadini
Achille
A
Azzena
Gian Battista
GB
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000528:radiation effects*; D020864:Calcium Channels, N-Type / Q000528:radiation effects*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D004574:Electromagnetic Fields; D004594:Electrophysiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011691:Puromycin / Q000494:pharmacology; D051381:Rats
D000964:Antimetabolites, Antineoplastic; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D016877:Oxidants; D011691:Puromycin; D006861:Hydrogen Peroxide; D002118:Calcium