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The intracellular loop between domains I and II of the B type calcium channel confers aspects of G protein sensitivity to the E type calcium channel

Page, KM; Stephens, GJ; Berrow, NS; Dolphin, AC; (1997) The intracellular loop between domains I and II of the B type calcium channel confers aspects of G protein sensitivity to the E type calcium channel. Journal of Neuroscience , 17 1330 - 1338. Green open access

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Abstract

Neuronal voltage-dependent calcium channels undergo inhibitory modulation by G-protein activation, generally involving both kinetic slowing and steady-state inhibition. We have shown previously that the b-subunit of neuronal calcium channels plays an important role in this process, because when it is absent, greater receptor-mediated inhibition is observed (Campbell et al., 1995b). We therefore hypothesized that the calcium channel b-subunits normally may occlude G-proteinmediated inhibition. Calcium channel b-subunits bind to the cytoplasmic loop between transmembrane domains I and II of the a1-subunits (Pragnell et al., 1994). We have examined the hypothesis that this loop is involved in G-protein-mediated inhibition by making chimeras containing the I–II loop of a1B or a1A inserted into a1E (a1EBE and a1EAE, respectively). This strategy was adopted because a1B (the molecular counterpart of N-type channels) and, to a lesser extent, a1A (P/Q-type) are G-protein-modulated, whereas this has not been observed to any great extent for a1E. Although a1B, coexpressed with a2-d and b1b transiently expressed in COS-7 cells, showed both kinetic slowing and steady-state inhibition when recorded with GTPgS in the patch pipette, both of which were reversed with a depolarizing prepulse, the chimera a1EBE (and, to a smaller extent, a1EAE) showed only kinetic slowing in the presence of GTPgS, and this also was reversed by a depolarizing prepulse. These results indicate that the I–II loop may be the molecular substrate of kinetic slowing but that the steady-state inhibition shown by a1B may involve a separate site on this calcium channel.

Type: Article
Title: The intracellular loop between domains I and II of the B type calcium channel confers aspects of G protein sensitivity to the E type calcium channel
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The license allows you to copy, distribute, and transmit the work, as well as adapting it. However, you must attribute the work to the author (but not in any way that suggests that they endorse you or your use of the work), and cannot use the work for commercial purposes without prior permission of the author. If you alter or build upon this work, you can distribute the resulting work only under the same or similar license to this one. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA.
Keywords: calcium
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/131340
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