TY - JOUR
T1 - CNTF inhibits high voltage activated Ca2+ currents in fetal mouse cortical neurones.
AU - Holm, Ninna R
AU - Christophersen, Palle
AU - Hounsgaard, Jørn
AU - Gammeltoft, Steen
AU - Olesen, Søren-Peter
N1 - Keywords: Animals; Calcium; Calcium Channel Blockers; Calcium Channels; Cells, Cultured; Cerebral Cortex; Ciliary Neurotrophic Factor; GTP-Binding Proteins; Glycosylphosphatidylinositols; Insulin-Like Growth Factor I; Mice; Mice, Inbred Strains; Neurons; Neurotrophin 3; Patch-Clamp Techniques; Pertussis Toxin; Phosphatidylinositol Diacylglycerol-Lyase; Receptor, Ciliary Neurotrophic Factor; Signal Transduction; Type C Phospholipases; Virulence Factors, Bordetella
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 12153474
SN - 0022-3042
VL - 82
SP - 495
EP - 503
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 3
ER -