title: T-Type calcium channel alpha1G and alpha1H subunits in human retinoblastoma cells and their loss after differentiation.
abstract: 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 Ba(2+)-containing bath solutions, the current has an activation midpoint near -25 mV and appears to be fully inactivated at -20 mV. Sr(2+) and Ca(2+) are preferred charge carriers relative to Ba(2+), and the current vanishes in the absence of these divalent cations. Cd(2+) blocks the current with an IC(50) of 160 microM, and Ni(2+) blocks in a biphasic manner with IC(50)s of 22 and 352 microM. The current is unaffected when sodium is replaced with other monovalent cations, and it is insensitive to nifedipine, omega-conotoxin GVIA, omega-agatoxin IVA, and omega-conotoxin MVIIC. RT-PCR revealed the presence of alpha 1G and alpha 1H mRNA in undifferentiated cells, but following differentiation, a striking reduction of both alpha 1G and alpha 1H mRNA was found, and this was paralleled by the loss of T-type Ca channel currents. alpha 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 alpha 1G and alpha 1H Ca channel subunit expression is reduced in cells that have differentiated and exited the cell cycle.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia B3H 4H7.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirooka
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Bertolesi
authors.forename: Melanie E M
authors.initials: ME
authors.lastname: Kelly
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Denovan-Wright
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Sun
authors.forename: Jawed
authors.initials: J
authors.lastname: Hamid
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Zamponi
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Juhasz
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Haynes
authors.forename: Steven
authors.initials: S
authors.lastname: Barnes
mesh_terms: D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002413:Cations, Divalent / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004553:Electric Conductivity; D004558:Electric Stimulation; D006801:Humans; D020748:Mibefradil / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D012175:Retinoblastoma / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002413:Cations, Divalent; D020033:Protein Isoforms; D020748:Mibefradil