The Journal of Neuroscience, September 15, 1998, 18(18):7372-7380
Reciprocal Regulation of Ciliary Neurotrophic Factor Receptors
and Acetylcholine Receptors during Synaptogenesis in Embryonic Chick
Atria
Xin
Wang and
Stanley W.
Halvorsen
Department of Biochemical Pharmacology, School of Pharmacy, State
University of New York at Buffalo, Buffalo, New York 14260-1200
Ciliary neurotrophic factor (CNTF) has been implicated in the
development, survival, and maintenance of a broad range of neurons and
glia in the peripheral nervous system and the CNS. Evidence also
suggests that CNTF may affect development of cells outside the nervous
system. We have found that functional CNTF and its receptor are
expressed in developing embryonic chick heart and may be involved in
parasympathetic synapse formation. CNTF and CNTF receptor mRNA levels
were highest at embryonic day 11 (E11)-E13, the period of
parasympathetic innervation in chick atria. Levels of atrial CNTF
receptor mRNA were fourfold greater at E13 than at E6 and at E13 were
2.5-fold higher in atria than in ventricle, corresponding to the higher
degree of parasympathetic innervation occurring in atria. Treatment of
isolated atria or cultured atrial myocytes with recombinant human or
avian CNTF resulted in the tyrosine phosphorylation and nuclear
translocation of the signal transducer and activator of transcription
STAT3. The developmental increase in atrial CNTF receptor mRNA
was enhanced by stimulating muscarinic receptors with carbachol
in ovo and was inhibited by blocking muscarinic
cholinergic receptors with atropine. Treatment of cultured atrial
myocytes with CNTF resulted in a twofold increase in the levels of
muscarinic receptors. Thus, CNTF was able to regulate a key component
of parasympathetic synapses on atrial myocytes. These results suggest a
postsynaptic role for CNTF in the onset of parasympathetic function in
the developing heart and provide new clues to molecular mechanisms
directing synapse formation at targets of the autonomic nervous
system.
Key words:
parasympathetic; STAT; CNTF; heart development; synapse
formation; cardiomyocyte; cytokines; receptor regulation
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