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Molecular and Cellular Biochemistry

, Volume 203, Issue 1–2, pp 23–31 | Cite as

Increased T-type Ca2+ channel activity as a determinant of cellular toxicity in neuronal cell lines expressing polyglutamine-expanded human androgen receptors

  • Adrian Sculptoreanu
  • Hanan Abramovici
  • Abdullah A.R. Abdullah
  • Anna Bibikova
  • Valerie Panet-Raymond
  • Dov Frankel
  • Hyman M. Schipper
  • Leonard Pinsky
  • Mark A. Trifiro
Article

Abstract

We have analyzed Ca2+ currents in two neuroblastoma-motor neuron hybrid cell lines that expressed normal or glutamine-expanded human androgen receptors (polyGln-expanded AR) either transiently or stably. The cell lines express a unique, low-threshold, transient type of Ca2+ current that is not affected by L-type Ca2+ channel blocker (PN 200-110), N-type Ca2+ channel blocker (ω-conotoxin GVIA) or P-type Ca2+ channel blocker (Agatoxin IVA) but is blocked by either Cd2+ or Ni2+. This pharmacological profile most closely resembles that of T-type Ca2+ channels [1-3]. Exposure to androgen had no effect on control cell lines or cells transfected with normal AR but significantly changed the steady-state activation in cells transfected with expanded AR. The observed negative shift in steady-state activation results in a large increase in the T-type Ca2+ channel window current. We suggest that Ca2+ overload due to abnormal voltage-dependence of transient Ca2+ channel activation may contribute to motor neuron toxicity in spinobulbar muscular atrophy (SBMA). This hypothesis is supported by the additional finding that, at concentrations that selectively block T-type Ca2+ channel currents, Ni2+ significantly reduced cell death in cell lines transfected with polyGln-expanded AR.

T-type Ca2+ channel polyglutamine-expanded androgen receptor CAG trinucleotide repeats spinobulbar muscular atrophy apoptosis motorneuron cell lines neuroblastoma 

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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Adrian Sculptoreanu
    • 1
    • 2
  • Hanan Abramovici
    • 3
  • Abdullah A.R. Abdullah
    • 1
    • 4
  • Anna Bibikova
    • 3
  • Valerie Panet-Raymond
    • 1
    • 4
  • Dov Frankel
    • 1
    • 5
  • Hyman M. Schipper
    • 1
    • 5
  • Leonard Pinsky
    • 1
    • 6
  • Mark A. Trifiro
    • 1
    • 7
  1. 1.Lady Davis Institute for Medical ResearchSMBD-Jewish General HospitalCanada
  2. 2.Department of Experimental Medicine and SurgeryMcGill UniversityMontrealCanada
  3. 3.Lady Davis Institute for Medical Research, SMBD-Jewish General HospitalMcGill UniversityMontrealCanada
  4. 4.Department of BiologyMcGill UniversityMontrealCanada
  5. 5.Department of Neurology and NeurosurgeryMcGill UniversityMontrealCanada
  6. 6.Departments of Human Genetics, Medicine and BiologyMcGill UniversityMontrealCanada
  7. 7.Department of MedicineMcGill UniversityMontrealCanada

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