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The Journal of Neuroscience, August 1, 2000, 20(15):5616-5622
Developmental Regulation of Neuronal KCa Channels by
TGF 1: Transcriptional and Posttranscriptional Effects Mediated by
Erk MAP Kinase
Loic
Lhuillier and
Stuart E.
Dryer
Department of Biology and Biochemistry, University of Houston,
Houston, Texas 77204-5513
An avian ortholog of transforming growth factor  1
(TGF1) is the target-derived factor responsible for the
developmental expression of large-conductance
Ca2+-activated K+
(KCa) channels in chick ciliary ganglion (CG)
neurons developing in vivo and in vitro.
Application of TGF1 evokes an acute stimulation of KCa
that can be observed immediately after cessation of a 12 hr exposure to
this factor, that persists in the presence of protein synthesis
inhibitors, and that is therefore mediated by posttranslational events.
Here we show that a single 3 hr exposure to TGF1 can also induce
long-lasting stimulation of macroscopic KCa that persists for at least 3.5 d after the end of the treatment. In contrast to
the acute stimulation, this sustained effect is dependent on the
transcription and synthesis of new proteins at approximately the time
of TGF1 treatment. However TGF1 does not cause increases in the
levels of slowpoke  subunit transcripts in CG
neurons, suggesting that induction of some other protein or proteins is required for sustained enhancement of macroscopic KCa. In
addition, application of TGF1 evoked an almost immediate but
transient phosphorylation of the mitogen-activated protein kinase
Erk in CG neurons. TGF1-evoked Erk activation was blocked by the
specific MEK1 inhibitor
2- (2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059).
Moreover, application of PD98059 blocked both acute and sustained
KCa stimulation evoked by TGF1. These results indicate that TGF1 elicits a biphasic stimulation of KCa via
activation of an MEK1-Erk pathway and raise the possibility that other
neuronal effects of TGF superfamily members entail Erk activation.
Key words:
TGF; slowpoke; trophic factor; MAP kinase; neuregulin; ciliary ganglion
Copyright © 2000 Society for Neuroscience 0270-6474/00/20155616-07$05.00/0
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