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Calcium induced calcium release in proximity to hair cell BK channels revealed by PKA activation

Jun-ping Bai, Na Xue, Omolara Lawal, Anda Nyati, Joseph Santos-Sacchi, Dhasakumar Navaratnam
doi: https://doi.org/10.1101/2019.12.30.890558
Jun-ping Bai
aDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA
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Na Xue
eDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Omolara Lawal
aDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA
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Anda Nyati
fUndergraduate Program, Johns Hopkins University, Baltimore, MD, USA
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Joseph Santos-Sacchi
bDepartment of Surgery, Yale School of Medicine, New Haven, CT, USA
cDepartment of Cell and Molecular Physiology, Yale School of Medicine, New Haven, CT, USA
dDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA
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Dhasakumar Navaratnam
aDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA
bDepartment of Surgery, Yale School of Medicine, New Haven, CT, USA
dDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA
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  • For correspondence: Dhasakumar.Navaratnam@Yale.Edu
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Abstract

Large conductance calcium-activated potassium (BK) channels play a critical role in electrical resonance, a mechanism of frequency selectivity in chicken hair cells. We determine that BK currents are dependent on inward flow of Ca2+, and intracellular buffering of Ca2+. Entry of Ca2+ is further amplified locally by Ca2+ induced Ca2+ release (CICR) in close proximity to plasma membrane BK channels. Ca2+ imaging reveals peripheral clusters of high concentrations of Ca2+ that are suprathreshold to that needed to activate BK channels. PKA activation increases BK currents likely by recruiting more BK channels due to spatial spread of high Ca2+ concentrations in turn from increasing CICR. STORM imaging confirms the presence of nanodomains with ryanodine and IP3 receptors in close proximity to the Slo subunit of BK channels. Together, these data require a rethinking of how electrical resonance is brought about and suggest effects of CICR in synaptic release. Both genders were included in this study.

Footnotes

  • Figures 2-5 have been revised to include G-V relationships in the different experimental conditions. The methods have been clarified to include this additional data. The results and discussion too have been changed to include these data.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 24, 2020.
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Calcium induced calcium release in proximity to hair cell BK channels revealed by PKA activation
Jun-ping Bai, Na Xue, Omolara Lawal, Anda Nyati, Joseph Santos-Sacchi, Dhasakumar Navaratnam
bioRxiv 2019.12.30.890558; doi: https://doi.org/10.1101/2019.12.30.890558
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Calcium induced calcium release in proximity to hair cell BK channels revealed by PKA activation
Jun-ping Bai, Na Xue, Omolara Lawal, Anda Nyati, Joseph Santos-Sacchi, Dhasakumar Navaratnam
bioRxiv 2019.12.30.890558; doi: https://doi.org/10.1101/2019.12.30.890558

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