title: CNTF inhibits high voltage activated Ca2+ currents in fetal mouse cortical neurones.
abstract: Neurotrophic factors yield neuroprotection by mechanisms that may be related to their effects as inhibitors of apoptosis as well as their effects on ion channels. The effect of ciliary neurotrophic factor (CNTF) on high-threshold voltage-activated Ca channels in cultured fetal mouse brain cortical neurones was investigated. Addition of CNTF into serum-free growth medium resulted in delayed reduction of the Ca2+ currents. The currents decreased to 50% after 4 h and stabilized at this level during incubation with CNTF for 48 h. Following removal of CNTF the inhibition was completely reversed after 18 h. CNTF reduced the current of all pharmacological subtypes of Ca channels as shown by use of selective blockers of L, N, and P/Q type Ca channels (nifedipine, omega-conotoxin MVIIA, omega-agatoxin IVA). The Ca channel depression was mediated via the CNTF receptor, because enzymatic cleavage of the alpha-subunit glycerophosphatidylinositol anchor of the receptor eliminated the response. The CNTF effect was not elicited through pertussis toxin-sensitive G proteins. Other neurotrophic factors like neurotrophin-3 and insulin-like growth factor-I had no effect on the Ca2+ currents. These results may have important implications for the possible functions of CNTF in the nervous system, such as altered synaptic activity, neuronal excitability and susceptibility to brain ischaemia.
authors.affiliation: NeuroSearch, Pederstrupvej, Ballerup, Denmark.
authors.forename: Ninna R
authors.initials: NR
authors.lastname: Holm
authors.forename: Palle
authors.initials: P
authors.lastname: Christophersen
authors.forename: Jørn
authors.initials: J
authors.lastname: Hounsgaard
authors.forename: Steen
authors.initials: S
authors.lastname: Gammeltoft
authors.forename: Søren-Peter
authors.initials: SP
authors.lastname: Olesen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D020801:Receptor, Ciliary Neurotrophic Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020934:Ciliary Neurotrophic Factor; D017261:Glycosylphosphatidylinositols; D020933:Neurotrophin 3; D020801:Receptor, Ciliary Neurotrophic Factor; D010566:Virulence Factors, Bordetella; D007334:Insulin-Like Growth Factor I; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D002118:Calcium