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CNTF inhibits high voltage activated Ca 2+ currents in fetal mouse cortical neurones
Author(s) -
Holm Ninna R.,
Christophersen Palle,
Hounsgaard Jørn,
Gammeltoft Steen,
Olesen SørenPeter
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00963.x
Subject(s) - ciliary neurotrophic factor , chemistry , medicine , neuroprotection , nerve growth factor , endocrinology , voltage dependent calcium channel , neurotrophin , neurotrophic factors , neuroscience , receptor , biology , calcium , biochemistry
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 Ca 2+ 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, ω‐conotoxin MVIIA, ω‐agatoxin IVA). The Ca channel depression was mediated via the CNTF receptor, because enzymatic cleavage of the α‐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 Ca 2+ 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.