The Journal of Membrane Biology

, Volume 237, Issue 2–3, pp 59–69 | Cite as

Biophysical Properties of Human Medulloblastoma Cells

  • Nola Jean Ernest
  • Naomi J. Logsdon
  • Michael B. McFerrin
  • Harald Sontheimer
  • Susan E. Spiller
Article

Abstract

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

Keywords

Medulloblastoma Membrane biophysics Calcium-activated K+ channel Modulation of neuronal ion channel 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Nola Jean Ernest
    • 1
    • 2
  • Naomi J. Logsdon
    • 1
  • Michael B. McFerrin
    • 2
    • 3
  • Harald Sontheimer
    • 2
    • 3
  • Susan E. Spiller
    • 1
    • 2
  1. 1.Department of PediatricsUniversity of Alabama School of MedicineBirminghamUSA
  2. 2.Civitan International Research CenterUniversity of Alabama School of MedicineBirminghamUSA
  3. 3.Department of NeurobiologyUniversity of Alabama School of MedicineBirminghamUSA

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