Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage
- University of Washington, United States
- University of California, Davis, United States
Abstract
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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Author details
Funding
National Institute of Neurological Disorders and Stroke (R37NS008174)
- Bertil Hille
National Heart, Lung, and Blood Institute (R01HL085686)
- Luis F Santana
Wayne E. Crill Endowed Professorship (Professor Fellowship)
- Bertil Hille
National Heart, Lung, and Blood Institute (R01HL085870)
- Luis F Santana
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animals were handled according to guidelines approved by the University of Washington Institutional Animal Care and Use Committee (#2084-03).
Copyright
© 2017, Vivas et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage
eLife 6:e28029.
https://doi.org/10.7554/eLife.28029
