Document Detail


Biophysical properties of human medulloblastoma cells.
MedLine Citation:
PMID:  20931182     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Medulloblastoma is a pediatric high-grade cerebellar malignancy derived from neuronal precursors. Although electrophysiologic characteristics of cerebellar granule neurons at all stages of cell development have been well described, such characterization has not been reported for medulloblastoma. In this study we attempt to characterize important electrophysiologic features of medulloblastoma that may distinguish it from the surrounding cerebellum. Using patient-derived cell lines and tumor tissues, we show that medulloblastoma cells have no inward Na+ current or transient K+ current involved in action potential generation and propagation, typically seen in granule neurons. Expression and function of calcium-activated, large-conductance K+ channels are diminished in medulloblastoma, judged by electrophysiology and Western analysis. The resting membrane potential of medulloblastoma cells in culture is quite depolarized compared to granule neurons. Interestingly, medulloblastoma cells express small, fast-inactivating calcium currents consistent with T-type calcium channels, but these channels are activated only from hyperpolarized potentials, which are unlikely to occur. Additionally, a background acid-sensitive K+ current is present with features characteristic of TASK1 or TASK3 channels, such as inhibition by ruthenium red. Western analysis confirms expression of TASK1 and TASK3. In describing the electrophysiologic characteristics of medulloblastoma, one can see features that resemble other high-grade malignancies as opposed to normal cerebellar granule neurons. This supports the notion that the malignant phenotype of medulloblastoma is characterized by unique changes in ion channel expression.
Authors:
Nola Jean Ernest; Naomi J Logsdon; Michael B McFerrin; Harald Sontheimer; Susan E Spiller
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-08
Journal Detail:
Title:  The Journal of membrane biology     Volume:  237     ISSN:  1432-1424     ISO Abbreviation:  J. Membr. Biol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0211301     Medline TA:  J Membr Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  59-69     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University of Alabama School of Medicine, 1719 6th Ave. S., CIRC 252A, Birmingham, AL 35294, USA.
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
R01NS31234/NS/NINDS NIH HHS

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