Faculty Collaboration Database

Differentiated dopaminergic MN9D cells only partially recapitulate the electrophysiological properties of midbrain dopaminergic neurons. Dev Neurosci 2006;28(6):528-37

Date

10/10/2006

Pubmed ID

17028430

DOI

10.1159/000095115

Scopus ID

2-s2.0-33749560870 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

The cell line MN9D, a fusion of embryonic ventral mesencephalic and neuroblastoma cells, is extensively used as a model of dopamine (DA) neurons because it expresses tyrosine hydroxylase and synthesizes and releases DA. These cells are also used to test mechanisms and potential therapeutics relevant to the loss of DA neurons in Parkinson's disease. To date, little work has been done to determine whether MN9D cells electrophysiologically resemble mature DA neurons. We examined sodium, calcium and potassium currents in undifferentiated and differentiated MN9D cells, and compared these to those found in acutely dissociated mouse substantia nigra pars compacta DA neurons. It was observed that undifferentiated MN9D cells bore no resemblance to DA neurons. Upon differentiation with butyric acid with or without a prior treatment with glial cell line-derived neurotrophic factor, differentiated MN9D cells produce an electrophysiological profile that more closely resembles substantia nigra pars compacta DA neurons even though the A-type potassium current remains noticeably absent. These observations demonstrate that undifferentiated MN9D cells are not reasonable models of DA neurons. Although differentiated MN9D cells are closer to the mature DA neuronal phenotype, they do not fully mimic DA neurons and are likely to be of questionable value as a model because of their substantive differences, including the lack of the characteristic A-type potassium current. The future use of one or a combination of growth or other factors to differentiate MN9D cells may yield a more useful model system for Parkinson's disease studies in vitro.

Author List

Rick CE, Ebert A, Virag T, Bohn MC, Surmeier DJ

Author

Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Butyric Acid
Calcium Channels
Cell Differentiation
Cell Line
Dopamine
Glial Cell Line-Derived Neurotrophic Factor
Hybridomas
Ion Channels
Male
Membrane Potentials
Mice
Mice, Inbred C57BL
Neurons
Potassium Channels
Sodium Channels
Stem Cells
Substantia Nigra
Synaptic Transmission