Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage

CaV-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 CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3...

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Vydáno v:eLife Ročník 6
Hlavní autoři: Vivas, Oscar, Moreno, Claudia M, Santana, Luis F, Hille, Bertil
Médium: Journal Article
Jazyk:angličtina
Vydáno: Cambridge eLife Sciences Publications Ltd 30.06.2017
eLife Sciences Publications, Ltd
Témata:
Biophysics and Structural Biology
BK channels
Calcium channels (voltage-gated)
Calcium influx
Channel gating
Excitability
ground-state depletion
hippocampal neurons
Hippocampus
Hypotheses
Immunoglobulins
Localization
Physiology
Plasmids
Potassium
Potassium channels (calcium-gated)
Software
super-resolution microscopy
Sympathetic nerves
sympathetic neurons
voltage-gated calcium channels
ISSN:2050-084X, 2050-084X
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Shrnutí:CaV-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 CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 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 CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 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 CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials.
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These authors contributed equally to this work.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.28029