Nerve growth factor regulates sodium but not potassium channel currents in sympathetic B neurons of adult bullfrogs.
The TTX-sensitive and -resistant components of the voltage-gated Na(+) current (TTX-s I(Na) and TTX-r I(Na)) are increased within 2 wk of cutting the axons of B-cells in bullfrog paravertebral sympathetic ganglia (BFSG). Axotomy also increases the noninactivating, voltage-activated K(+) current (M current I(M)), whereas delayed rectifier K(+) current (I(K)) is reduced. We found that similar effects were produced when BFSG B cells were dissociated from adult bullfrogs and maintained in a defined-medium, neuron-enriched, low-density, serum-free culture. Thus the density of TTX-s I(Na), TTX-r I(Na), and I(M) were transiently increased, whereas I(K) density was decreased. Reduction in voltage-sensitive, Ca(2+)-dependent K(+) current (I(C)) was attributed to previously documented decreases in Ca(2+) channel current (I(Ca)). To test whether axotomy- or culture-induced changes in ion channel function reflect loss of retrograde influence of nerve growth factor (NGF), we examined the effect of murine beta-NGF on TTX-s I(Na), TTX-r I(Na), I(K), and I(M). Culture of neurons for 15 days in the presence of NGF (200 ng/ml), more than doubled total I(Na) density but did not enhance neurite outgrowth. The TTX-r I(Na) density was increased about threefold and the TTX-s I(Na) density increased 2.4-fold. NGF did not affect the activation or inactivation kinetics of the total Na(+) conductance. Effects of NGF were blocked by the transcription inhibitors, cordycepin (20 microM) and actinomycin D (0.01 microg/ml). I(K) and I(M) were unaffected by NGF, and although I(C) was enhanced, this likely reflected the known effect of NGF on I(Ca) in BFSG neurons. Na(+) channel synthesis and/or expression in adult sympathetic neurons is therefore subject to selective regulation by NGF. Despite this, the increase in I(Na) and I(M) as well as the decrease in I(K) seen in BFSG neurons in culture or after axotomy cannot readily be explained in terms of alterations in the availability of target-derived NGF.
Lei
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Department of Pharmacology and University Centre for Neuroscience, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Dryden
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Smith
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PA
D000367:Age Factors; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019771:Axotomy; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels; D003839:Deoxyadenosines / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011892:Rana catesbeiana; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D000970:Antineoplastic Agents; D051668:Delayed Rectifier Potassium Channels; D003839:Deoxyadenosines; D019384:Nucleic Acid Synthesis Inhibitors; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels; D003609:Dactinomycin; D013779:Tetrodotoxin; D020932:Nerve Growth Factor; D012964:Sodium; C058120:cordycepin; D011188:Potassium