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The Journal of Neurophysiology Vol. 88 No. 1 July 2002, pp. 196-205
Copyright ©2002 by the American Physiological Society
1G and
1H Subunits in Human
Retinoblastoma Cells and Their Loss After Differentiation
1Department of Physiology and Biophysics, 2Department of Ophthalmology, and 3Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia B3H 4H7; and 4Neuroscience Research Group, University of Calgary, Calgary, Alberta T2N 4N1, Canada
Hirooka, Kazuyuki,
Gabriel E. Bertolesi,
Melanie E. M. Kelly,
Eileen M. Denovan-Wright,
Xiaolu Sun,
Jawed Hamid,
Gerald W. Zamponi,
Alexander E. Juhasz,
Lawrence W. Haynes, and
Steven Barnes.
T-Type Calcium Channel
1G and
1H Subunits in Human
Retinoblastoma Cells and Their Loss After Differentiation. J. Neurophysiol. 88: 196-205, 2002. Human
retinoblastoma cells are multipotent retinal precursor cells capable of
differentiating into photoreceptors, neurons, and glia. The
current-voltage relation of the undifferentiated cells is dominated by
a transient inward current that disappears shortly after
differentiation. In 20 mM Ba2+-containing bath
solutions, the current has an activation midpoint near
25 mV and
appears to be fully inactivated at
20 mV. Sr2+
and Ca2+ are preferred charge carriers relative
to Ba2+, and the current vanishes in the absence
of these divalent cations. Cd2+ blocks the
current with an IC50 of 160 µM, and
Ni2+ blocks in a biphasic manner with
IC50s of 22 and 352 µM. The current is
unaffected when sodium is replaced with other monovalent cations, and
it is insensitive to nifedipine,
-conotoxin GVIA,
-agatoxin IVA,
and
-conotoxin MVIIC. RT-PCR revealed the presence of
1G and
1H mRNA in undifferentiated cells, but following differentiation, a
striking reduction of both
1G and
1H mRNA was found, and this was
paralleled by the loss of T-type Ca channel currents.
1I subunit
mRNA levels were low in undifferentiated and differentiated cells.
These results suggest that T-type Ca channels could play a role in
undifferentiated retinoblastoma cell physiology since
1G and
1H
Ca channel subunit expression is reduced in cells that have
differentiated and exited the cell cycle.
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