Ceruloplasmin: an endogenous depolarizing factor in neurons?
The biological effects of ceruloplasmin have been exclusively ascribed to its roles as a copper carrier and an antioxidant. Although neuronal involvement of ceruloplasmin is closely related to aging and certain neuronal disorders, neuronal effects of ceruloplasmin are unknown and the possible modulation of membrane potential and ion channels by ceruloplasmin has not been investigated. In the present study, the membrane electrical properties of neuroblastoma cells in the presence of ceruloplasmin were studied using the patch-clamp technique. Ceruloplasmin induced a rapid and sustained membrane depolarization. This capacity of ceruloplasmin was abolished either when the copper was removed from ceruloplasmin or when ceruloplasmin was heat-inactivated. The depolarizing effect of ceruloplasmin was not due to an enhanced Ca2+ or Na+ influx but it seemed to result from a reduced K+ efflux since ceruloplasmin significantly inhibited a TEA-sensitive delayed rectifier K+ channel. To our knowledge, this is the first report which indicates that ceruloplasmin is an endogenous neuronal depolarizing factor.
Wang
R
R
Department of Physiology, Université de Montréal, Canada.
Zhang
L
L
Mateescu
M A
MA
Nadeau
R
R
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002570:Ceruloplasmin / Q000494:pharmacology*; D051668:Delayed Rectifier Potassium Channels; D006801:Humans; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D012964:Sodium / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013757:Tetraethylammonium Compounds; C028521:lanthanum chloride; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D007811:Lanthanum; D012964:Sodium; D002570:Ceruloplasmin; D011188:Potassium; D002118:Calcium