Dynamic association of calcium channel subunits at the cellular membrane

Andreas Voigt; Romy Freund; Jennifer Heck; Markus Missler; Gerald J. Obermair; Ulrich Thomas; Martin Heine

doi:10.1117/1.NPh.3.4.041809

3 November 2016 Dynamic association of calcium channel subunits at the cellular membrane

Andreas Voigt, Romy Freund, Jennifer Heck, Markus Missler, Gerald J. Obermair, Ulrich Thomas, Martin Heine

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Funded by: Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence “Hearing4all”

Neurophotonics, Vol. 3, Issue 4, 041809 (November 2016). https://doi.org/10.1117/1.NPh.3.4.041809

Abstract

High voltage gated calcium channels (VGCCs) are composed of at least three subunits, one pore forming α₁-subunit, an intracellular β-variant, and a mostly extracellular α₂δ-variant. Interactions between these subunits determine the kinetic properties of VGCCs. It is unclear whether these interactions are stable over time or rather transient. Here, we used single-molecule tracking to investigate the surface diffusion of α₁- and α₂δ₁-subunits at the cell surface. We found that α₂δ₁-subunits show higher surface mobility than α₁-subunits, and that they are only transiently confined together, suggesting a weak association between α₁- and α₂δ₁-subunits. Moreover, we observed that different α₁-subunits engage in different degrees of association with the α₂δ₁-subunit, revealing the tighter interaction of α₂δ₁ with Ca_V1.2<Ca_V2.2<Ca_V2.1<Ca_V3.2. These data indicate a distinct regulation of the α₁/α₂δ₁ interaction in VGCC subtypes. We modeled their membrane dynamics in a Monte Carlo simulation using experimentally determined diffusion constants. Our modeling predicts that the ratio of associated α₁- and α₂δ₁-subunits mainly depends on their expression density and confinement in the membrane. Based on the different motilities of particular α₁/α₂δ₁-subunit combinations, we propose that their dynamic assembly and disassembly represent an important mechanism to regulate the signaling properties of VGCC.

CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Andreas Voigt, Romy Freund, Jennifer Heck, Markus Missler, Gerald J. Obermair, Ulrich Thomas, and Martin Heine "Dynamic association of calcium channel subunits at the cellular membrane," Neurophotonics 3(4), 041809 (3 November 2016). https://doi.org/10.1117/1.NPh.3.4.041809

Published: 3 November 2016

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