Altered calcium currents in cultured sensory neurons of normal and trisomy 16 mouse fetuses, an animal model for human trisomy 21 (Down syndrome).
Down syndrome is determined by the presence of an extra copy of autosome 21 and is expressed by multiple abnormalities, with mental retardation being the most striking feature. The condition results in altered electrical membrane properties of fetal dorsal root ganglia (DRG) neurons, as in the trisomy 16 fetal mouse, an animal model of the human condition. Cultured trisomic DRG neurons from human and mouse fetuses present faster rates of depolarization and repolarization in the action potential compared to normal controls and a shorter spike duration. Also, trisomy 16 brain and spinal cord tissue exhibit reduced acetylcholine secretion. Therefore, we decided to study Ca2+ currents in cultured DRG neurons from trisomy 16 and age-matched control mice, using the whole-cell patch-clamp technique. Trisomic neurons exhibited a 62% reduction in Ca2+ current amplitude and reduced voltage dependence of current activation at -30 and -20 mV levels. Also, trisomic neurons showed slower activation kinetics for Ca2+ currents, with up to 80% increase in time constant values. Kinetics of the inactivation phase were similar in both conditions. The results indicate that murine trisomy 16 alter Ca2+ currents, which may contribute to impaired cell function, including neurotransmitter release. These abnormalities also may alter neural development.
Caviedes
Pablo
P
Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile. pcaviede@med.uchile.cl
Caviedes
Raúl
R
Rapoport
Stanley I
SI
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000503:physiopathology*; D004558:Electric Stimulation; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000737:chemistry*; D018408:Patch-Clamp Techniques; D014314:Trisomy / Q000503:physiopathology*
D015220:Calcium Channels