Glycosylation is required for maintenance of functional voltage-activated channels in growing neocortical neurons of the rat.
Voltage-activated currents were studied in whole-cell patch-clamped rat neocortical neurons growing in culture and treated with tunicamycin (TU), an inhibitor of protein N-glycosylation. The size of the Na+ current decreased progressively in the presence of TU (1-2 microM). This decrease was faster in growing 5-14 day-old neurons (to ca. 40% of control after 24 hours of treatment) than in fully grown 20-40-day-old neurons (to ca. 40% of control after 68 hours of treatment). The fast transient K+ current (A-current) was abolished, and the delayed rectifier K+ current was markedly reduced by a 24 hour treatment with TU (1-2 microM) in growing neurons. In contrast, in fully grown neurons these currents were unaffected by the same TU treatment. The size of the Ca2+ current was significantly reduced following a 24 hour treatment with TU (1-2 microM) in neurons at early stages of differentiation, but remained stable in 20-40-day-old neurons. It is concluded that protein glycosylation, presumably of the channel proteins themselves, is important for the functional expression of voltage-activated channels in embryonic cortical neurons during the early stages of cell growth in culture; the channels become less dependent on glycosylation in mature neurons.
Zona
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C
Dipartimento di Medicina Sperimentale e Scienze Biochemiche, Università Roma Tor Vergata, Italy.
Eusebi
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Miledi
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R
D000375:Aging; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development* / Q000502:physiology; D004622:Embryo, Mammalian; D006031:Glycosylation; D007473:Ion Channels / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D014415:Tunicamycin / Q000494:pharmacology
D015220:Calcium Channels; D007473:Ion Channels; D008565:Membrane Proteins; D015221:Potassium Channels; D015222:Sodium Channels; D014415:Tunicamycin