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J Mol Neurosci 1997, 8, 115-130
Culture density regulates both the cholinergic phenotype and the expression of the CNTF receptor in P19 neurons.
Parnas D, Linial M
The P19 embryonal carcinoma cells differentiate into neurons,
astrocytes, and fibroblast-like cells following induction with retinoic acid.
The cells mature into functional neurons, as determined by their ability to
release neurotransmitters in a Ca(2+)- and depolarization-dependent manner.
P19 neurons in culture represent a mixed population in terms
of their neurotransmitter phenotype. The cholinergic phenotype of these neurons
is modulated by culture density. Cholinergic markers, such as the vesicular
acetylcholine transporter, acetyl cholinesterase, and choline acetyltransferase,
are expressed in about 85% of the cells in sparse cultures and are
largely suppressed at high cell densities.
In contrast, glutamate release is enhanced in dense P19
neuronal cultures. The factor mediating the density effect is
concentrated exclusively on the cell membrane of P19 neurons and not on
the nonneuronal cells, which also differentiate from P19 embryonal
This membrane-associated component retains its functionality,
even after membrane fixation. The downregulation of the cholinergic properties
in dense cultures is paralleled by a downregulation of the alpha subunit of
the ciliary neurotrophic factor (CNTF) receptor.
Thus, it is suggested that the membrane-associated factor,
which mediates the density effect, downregulates the cholinergic phenotype by
inhibiting the responsiveness of these neurons to CNTF. We further suggest that
the P19 cell line can serve as a model system for the study of neurotransmitter
phenotype acquisition and plasticity throughout neuronal differentiation.