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Proximal clustering between BK and Ca(V)1.3 channels promotes functional coupling and BK channel activation at low voltage

Ca(V)-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and Ca(V)1.3 channels, unique Ca(V)1 channels that activate at low voltages. We found that when BK and...

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Detalles Bibliográficos
Autores principales: Vivas, Oscar, Moreno, Claudia M, Santana, Luis F, Hille, Bertil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503510/
https://www.ncbi.nlm.nih.gov/pubmed/28665272
http://dx.doi.org/10.7554/eLife.28029
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author Vivas, Oscar
Moreno, Claudia M
Santana, Luis F
Hille, Bertil
author_facet Vivas, Oscar
Moreno, Claudia M
Santana, Luis F
Hille, Bertil
author_sort Vivas, Oscar
collection PubMed
description Ca(V)-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and Ca(V)1.3 channels, unique Ca(V)1 channels that activate at low voltages. We found that when BK and Ca(V)1.3 channels were co-expressed in the same cell, BK channels started activating near −50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated Ca(V)2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of Ca(V)1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of Ca(V)1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials. DOI: http://dx.doi.org/10.7554/eLife.28029.001
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spelling pubmed-55035102017-07-12 Proximal clustering between BK and Ca(V)1.3 channels promotes functional coupling and BK channel activation at low voltage Vivas, Oscar Moreno, Claudia M Santana, Luis F Hille, Bertil eLife Biophysics and Structural Biology Ca(V)-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and Ca(V)1.3 channels, unique Ca(V)1 channels that activate at low voltages. We found that when BK and Ca(V)1.3 channels were co-expressed in the same cell, BK channels started activating near −50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated Ca(V)2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of Ca(V)1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of Ca(V)1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials. DOI: http://dx.doi.org/10.7554/eLife.28029.001 eLife Sciences Publications, Ltd 2017-06-30 /pmc/articles/PMC5503510/ /pubmed/28665272 http://dx.doi.org/10.7554/eLife.28029 Text en © 2017, Vivas et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Vivas, Oscar
Moreno, Claudia M
Santana, Luis F
Hille, Bertil
Proximal clustering between BK and Ca(V)1.3 channels promotes functional coupling and BK channel activation at low voltage
title Proximal clustering between BK and Ca(V)1.3 channels promotes functional coupling and BK channel activation at low voltage
title_full Proximal clustering between BK and Ca(V)1.3 channels promotes functional coupling and BK channel activation at low voltage
title_fullStr Proximal clustering between BK and Ca(V)1.3 channels promotes functional coupling and BK channel activation at low voltage
title_full_unstemmed Proximal clustering between BK and Ca(V)1.3 channels promotes functional coupling and BK channel activation at low voltage
title_short Proximal clustering between BK and Ca(V)1.3 channels promotes functional coupling and BK channel activation at low voltage
title_sort proximal clustering between bk and ca(v)1.3 channels promotes functional coupling and bk channel activation at low voltage
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503510/
https://www.ncbi.nlm.nih.gov/pubmed/28665272
http://dx.doi.org/10.7554/eLife.28029
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